Early degradation and serum appearance of type I collagen fragments after myocardial infarction
|
|
- Vincent Charles
- 6 years ago
- Views:
Transcription
1 Journal of Molecular and Cellular Cardiology 36 (04) Brief Communication Early degradation and serum appearance of type I collagen fragments after myocardial infarction Francisco Villarreal a, *, Jeffrey Omens a, Wolfgang Dillmann a, Juha Risteli b, Judy Nguyen a, James Covell a a Department of Medicine, University of California, San Diego, CA, USA b Department of Clinical Chemistry, University of Oulu, Oulu and Kuopio University Hospital, Kuopio, Finland Received 24 November 03; received in revised form December 03; accepted 7 January 04 Abstract Although extracellular matrix-degrading enzymes matrix metalloproteinases (MMPs) are activated within minutes after myocardial infarction (MI), the time course of early MI-induced type I cardiac collagen degradation has not been assessed, nor has the ability of MMP inhibitor compounds, such as doxycycline (DOX), to limit these events. The objective of this study was to assess serum biomarker evidence of myocardial type I collagen degradation early (<48 h) after coronary occlusion (CO) and determine the capacity of DOX to ameliorate its release. CO studies were performed in untreated and DOX pre-treated pigs. Treated animals received DOX at 30 mg/kg/d. Radioimmunoassays were performed for serum levels of C-terminal telopeptide of collagen type I (ICTP) fragments. ICTP groups peaked by after MI. However, in DOX-treated animals, ICTP values returned to normal by 8 h. Average serum concentrations for ICTP values from 0 to 48 h post-mi were significantly inhibited by DOX treatment. In conclusion, serum biomarker results indicate that type I collagen degradation occurs within minutes after MI and that DOX likely reduces its degradation. 03 Elsevier Ltd. All rights reserved. Keywords: Collagen; Matrix metalloproteinases; Myocardial infarction; Doxycycline; Remodeling 1. Introduction Fibrillar collagen types I and III are the major types of extracellular matrix (ECM) proteins present in the heart [1]. Type I collagen comprises about 75% of myocardial collagens. Myocardial collagens provide structural support and integrity to the heart and allow for proper pump function. Matrix metalloproteinases (MMPs) are a family of zinccontaining endoproteinases whose main substrates are ECM proteins [2]. MMPs are secreted as zymogens and require activation to generate proteolytic activity [2]. In vivo studies have documented the time-dependent activation of MMPs following myocardial infarction (MI). Activation occurs within minutes, peaking approximately 1 2 d after MI and likely reflect the activation of pre-formed MMPs [3 6]. The time course of upregulation of MMP activity suggests that a significant amount of collagen degradation occurs very early (first 48 h) after MI. * Corresponding author. Tel: ; fax: address: fvillarr@ucsd.edu (F. Villarreal). Documenting the extent of damage to the cardiac ECM after ischemic injury has been difficult and most techniques require tissue samples [7,8]. The ability to perform serial serum determinations as done with biomarkers of cardiomyocyte damage would make it possible to assess not only the presence but also the time course and magnitude of MI-induced collagen degradation [9]. Serum marker radioimmunoassays (RIAs) that measure collagen degradation and/or synthesis are readily available and have been used in the setting of cardiovascular diseases [10,11]. When soft tissue type I collagen is exposed to active MMPs, a crosslinked C-terminal telopeptide of collagen type I (ICTP) is released that eventually reaches the bloodstream [10,11]. This marker can be used to monitor type I collagen degradation. Although serum evidence for MI-mediated release of cardiac type III collagen has been reported [11], nothing is known about ischemia-mediated damage to type I collagen. MMP inhibition following MI can preserve cardiac structure and function [12 ]. Doxycycline (DOX), a tetracycline derivative, is known to exert biological effects independent of its antimicrobial activity, including acting as a broad- 03 Elsevier Ltd. All rights reserved. doi:10.10/j.yjmcc
2 598 F. Villarreal et al. / Journal of Molecular and Cellular Cardiology 36 (04) spectrum MMP inhibitor [15 ]. We recently reported that short-term pre-treatment with DOX inhibits myocardial MMP activity, ameliorates post-mi remodeling and preserves passive ventricular function in rats []. Thus the ability to monitor collagen degradation after MI may also serve to test for effects that pharmacological therapies exert on type I collagen preservation. The objectives of this study were to assess for serum biomarker evidence of the early time course of cardiac type I collagen degradation after MI and to determine the capacity of DOX pre-treatment to ameliorate MI-induced increases in this biomarker. Results indicate that type I collagen degradation can be detected in serum 15 min after MI and that DOX significantly reduced type I collagen degradation. 2. Materials and methods 2.1. DOX treatment Male pigs weighing 25 kg were used. DOX was administered orally at 30 mg/kg/d. This DOX dose effectively blocks MMP activity in models of tissue injury and healing [17,]. Pre-treatment began 48 h prior to coronary occlusion (CO) and continued until 48 h after (end of study). Groups included sham (n = 3), control untreated (n = 6) and DOXtreated (n = 5) MIs. All procedures were approved by the Institutional Animal Care and Use Committee and conform to published NIH guidelines for animal research Surgical preparation Pigs underwent a thoracotomy to place a snare around the coronary artery 1 week prior to CO. Anesthesia was induced with ketamine (100 mg/kg) and xylazine (5 mg/kg), and maintained using isoflurane positive pressure ventilation. A left thoracotomy was performed and the pericardium opened. A suture running through a plastic tube was placed around a marginal branch of the circumflex artery. The plastic snare tube was buried subcutaneously. Catheters were placed in the jugular vein for blood sampling. Animals were allowed to recover from surgery for 1 week, at which time through a small incision the snare was exteriorized and occluded (except shams) using i.v. propofol anesthesia (2.5 mg/kg). Blood (serum) samples were collected at 48 h (pre-co), 24 h, 5, 15, 30 min, 1, 2, 3, 6, 8, 24 and 48 h after CO. Electrocardiograms were monitored for evidence of MI MI size determination Forty-eight hours after CO, animals were sacrificed, hearts excised and weighed. The left ventricle (LV) was cross-sectioned into 5 6 rings, which were stained in triphenyl tetrazolium chloride (TTC). Volumetric determinations of infarct size were performed by digital tracing of TTCstained sections. Formalin-fixed LV tissue was paraffin embedded for sectioning. Border zone myocardium sections were stained using either Masson s trichrome or anti-human ICTP antibodies ICTP determinations RIA (Orion Diagnostica) antibodies to human collagen I cross-react with pig [8]. Assays were performed as previously described and ICTP values were extrapolated from standard curves as ng/ml serum [8]. Data analysis included the computation of average ICTP levels over time from 5 min to 48 h post-co (i.e. area under the curve) [9] Statistical analysis Statistical analysis was performed using a Student s t-test. Results were considered to be statistically significant at P < Results Body weights for control and DOX-treated animals averaged 22.3 ± 2.8 and 24.2 ± 3.7 kg, respectively. Heart to body weight ratios 48 h after CO were 6.4 ± 1.1 for control and 6.3 ± 0.8 for DOX. MI size as a percent of LV mass was not significantly different between control (10.0 ± 2.7%) and DOX (11.5 ± 3.7%) groups. In all animals, elevated serum levels for ICTP were observed after thoracotomy (data not shown) and likely represent surgical trauma-induced increases and may explain the failure of previous studies to observe post-mi increases [8]. ICTP levels decreased in all animals by 7 d after the initial surgery to values comparable to those previously reported for normal (non-infarcted) pigs [8]. Fig. 1a shows ICTP levels for a representative sham animal, which did not increase relative to 5 min values. Fig. 1b illustrates representative changes in ICTP levels observed in a control CO animal. CO resulted in a rapid and sustained (up to 48 h) increase in serum ICTP levels, which peaked approximately after MI. Fig. 1c exemplifies changes in ICTP levels in a CO animal pre-treated with DOX. A rapid increase in ICTP levels was observed, peaking about after CO but returning to pre-occlusion levels by 8 h. On average, ICTP levels before CO were similar for both groups (15.6 ± 2.6 ng/ml for control and ± 3.3 ng/ml for DOX animals). ICTP values in control pigs peaked at 21.5 ± 2.5 ng/ml (P < 0.05 vs. pre-co) 6.4 ± 1.8 h post-co. DOX-treated pigs ICTP values peaked at 21.5 ± 3.4 ng/ml (P = 0.13 vs. pre-co) 5.8 ± 1.8 h post-co. Fig. 2 compares increases in ICTP levels in control and DOX animals. Sustained increases over time were observed in control animals peaking approximately 8 h post-co and partially returning towards pre-co levels by 24 and 48 h. In contrast, DOX pre-treated animals demonstrated an early increase in ICTP levels and a quick return to near pre-
3 F. Villarreal et al. / Journal of Molecular and Cellular Cardiology 36 (04) occlusion occlusion 8 h 1 day A. Sham 2 h 0.5 h 8 h 1 day pre-co level 2 day B. Control 5 min 2 h 2 day C. Doxycycline pre-co level 8 h 1 day 2 day Time (h) Fig. 1. Mean ICTP levels observed in single representative sham, control and DOX-treated infarcted pigs after CO. In contrast to sham pigs, control CO pigs yielded sustained increases in ICTP levels after infarction. With DOX treatment ICTP increases were of transient nature with values returning to pre-co levels by 8 h after infarction. occlusion values. Fig. 2 compares both groups in average ICTP serum values over time (5 min to 48 h area under the curve, panel B). DOX pre-treatment significantly inhibited average ICTP serum values over time (P < 0.05) yielding comparable values to shams. Fig. 3 shows that in areas of normal myocardium, collagen fibers stained light blue by Masson s trichrome. Collagen fibers continue to be evident without a discernible difference within the border zone and necrotic areas. However, with ICTP immunostaining intense red coloring (vector red) seen ICTP Avg. Conc. (ng/ml*hr) between myofibers in normal myocardium becomes less evident towards border zone areas and disappears in necrotic areas. 4. Discussion A. B. Time (h) CTRL DOX CONTROL DOX SHAM Fig. 2. Changes observed in ICTP levels with MI. (A) Differences in serum levels observed in control (n = 6) and DOX-treated (n = 5) animals from 5 min to 48 h after CO with significant differences observed at all time points except at 6 (P = 0.4) and 48 h (P = 0.). (B) Average concentration over time (area under the curve from panel A; mean ± S.E.M.) observed from 5 min to 48 h in all groups; * indicates significant differences vs. control (P < 0.05). In the setting of MI it has been demonstrated that MMP activation occurs by 10 min after CO [3 6]. However, evidence for ECM degradation has been more difficult to obtain. Whereas studies have provided evidence of damage to collagens after MI [7] none has provided information regarding type I collagen degradation, the time course of early events and the effects of drug therapy. The analysis of changes in ICTP levels indicated that MI yielded a significant increase which became evident as early as min, peaking approximately after CO. ICTP levels in untreated CO animals remained elevated and, in contrast to the DOX-treated group, failed to return to normal by 48 h. DOX pre-treatment significantly inhibited ICTP * *
4 600 F. Villarreal et al. / Journal of Molecular and Cellular Cardiology 36 (04) Fig. 3. Immunohistochemical evidence for collagen damage with MI. Left: section stained with Masson s trichrome. Collagen fibers (light blue) can be observed both in unaffected and necrotic myocardium. Right: a comparable, alternate section stained with anti-ictp. Whereas in normal muscle red staining can be observed, in necrotic tissue the reaction is negative (no ICTP detected). These results suggest that the source of increases in serum ICTP is the ischemic/necrotic myocardium. release over time in the infarcted animals. This finding gains relevance in light of various recent reports indicating that treatment with MMP inhibitors helps preserve cardiac structure and function after MI [12 ]. We reported that in rats subjected to CO, early (0 48 h), short-term pre-treatment with DOX inhibits MMP activation, preserves LV cardiac structure and passive function 4 weeks post-mi []. In this study we postulated that short-term pre-treatment with DOX may limit the greatest damage observed in collagen matrix while not interfering with subsequent increases (>48 h) in MMP activity which may compromise the ensuing wound healing response [19]. Results from this study and from ICTP RIA measurements emphasize the importance of early events in defining post-mi outcome. However, further long-term studies are needed to determine if DOX treatment affects ventricular remodeling given that MMP activation and collagen degradation may constitute necessary components of wound healing. Indeed, studies using rat models of MI have shown that peak increases in MMP gene expression and activity can occur well beyond 48 h []. Furthermore, increases in mrna levels for tissue inhibitor of MMPs (TIMPs) were noted to occur as early as after MI peaking by 48 h []. The use of anti-ictp on tissue sections clearly identifies damage to type I collagen by failing to stain areas of necrotic myocardium. The release of the 1/4 fragment from type I collagen denatures the protein structure yielding gelatin which is susceptible to further proteolytic degradation [11]. As such, collagen type I loses its characteristic mechanical (tensile) properties. Our observations imply that in the setting of infarction a major structural component of the cardiac ECM is significantly damaged and its function is likely compromised. These observations could be complemented in future studies by biochemical measurements of collagen content. The functional implications of degradation of the cardiac ECM after MI are important and deserve further examination. Our studies were limited to permanent CO and should be extended to assess the effect of other therapeutic interventions. Furthermore, the size of the MI induced in pigs was purposefully kept uniform and small; additional studies warrant the assessment of ICTP values with varying infarct sizes. The further validation of RIA for type I collagen peptides may allow their incorporation into clinical studies to assess the effects of various therapies on ECM degradation. References [1] Caulfield JB, Borg TK. The collagen network of the heart. Lab Invest 1979;40: [2] Nagase H, Woessner Jr JF. Matrix metalloproteinases. J Biol Chem 1999;274: [3] Etoh T, Joffs C, Deschamps AM, Davis J, Dowdy K, Hendrick J, et al. Myocardial and interstitial matrix metalloproteinase activity after acute myocardial infarction in pigs. Am J Physiol 01;281:H [4] Romanic AM, Burns-Kurtis CL, Gout B, Berrebi-Bertrand I, Ohlstein EH. Matrix metalloproteinase expression in cardiac myocytes following myocardial infarction in the rabbit. Life Sci 01;68: [5] Herzog E, Gu AG, Kohmoto T, Burkhoff D, Hochman JS. Early activation of metalloproteinases after experimental myocardial infarction occurs in infarct and non-infarct zones. Cardiovasc Pathol 1998; 7: [6] Danielsen CC, Wiggers H, Andersen HR. Increased amounts of collagenase and gelatinase in porcine myocardium following ischemia and reperfusion. J Mol Cell Cardiol 1998;30: [7] Takahashi S, Barry AC, Factor SM. Collagen degradation in ischaemic rat hearts. Biochem J 1990;265: [8] Wiggers H, Klebe T, Heickendorff L, Høst NB, Danielsen CC, Baandrup U, et al. Ischemia and reperfusion of the porcine myocardium: effect on collagen. J Mol Cell Cardiol 1997;29: [9] Uusimaa P, Risteli J, Niemelä M, Lumme J, Ikäheimo M, Jounela A, et al. Collagen scar formation after acute myocardial infarction: relationships to infarct size, left ventricular function, and coronary artery patency. Circulation 1997;96: [10] Risteli L, Risteli J. Noninvasive methods for detection of organ fibrosis. Boca Raton, FL: CRC Press; [11] Weber KT. Monitoring tissue repair and fibrosis from a distance [editorial; comment]. Circulation 1997;96: [12] Rohde LE, Ducharme A, Arroyo LH, Aikawa M, Sukhova GH, Lopez- Anaya A, et al. Matrix metalloproteinase inhibition attenuates early left ventricular enlargement after experimental myocardial infarction in mice. Circulation 1999;99: [13] Lindsey ML, Gannon J, Aikawa M, Schoen FJ, Rabkin E, Lopresti- Morrow L, et al. Selective matrix metalloproteinase inhibition reduces left ventricular remodeling but does not inhibit angiogenesis after myocardial infarction. Circulation 02;105:753 8.
5 F. Villarreal et al. / Journal of Molecular and Cellular Cardiology 36 (04) [] Yarbrough WM, Mukherjee R, Escobar GP, Mingoia JT, Sample JA, Hendrick JW, et al. Selective targeting and timing of matrix metalloproteinase inhibition in post-myocardial infarction remodeling. Circulation 03;108: [15] Golub LM, Lee HM, Ryan ME, Giannobile WV, Payne J, Sorsa T. Tetracyclines inhibit connective tissue breakdown by multiple nonantimicrobial mechanisms. Adv Dent Res 1998;12: [] Villarreal FJ, Griffin M, Omens J, Dillmann W, Nguyen J, Covell J. Early short-term treatment with doxycycline modulates postinfarction left ventricular remodeling. Circulation 03;108: [17] Curci JA, Petrinec D, Liao S, Golub LM, Thompson RW. Pharmacologic suppression of experimental abdominal aortic aneurysms: a comparison of doxycycline and four chemically modified tetracyclines. J Vasc Surg 1998;28: [] Lamparter S, Slight SH, Weber KT. Doxycycline and tissue repair in rats. J Lab Clin Med 02;139: [19] Heymans S, Luttun A, Nuyens D, Theilmeier G, Creemers E, Moons L, et al. Inhibition of plasminogen activators or matrix metalloproteinases prevents cardiac rupture but impairs therapeutic angiogenesis and causes cardiac failure. Nat Med 1999;5: [] Cleutjens J, Kandala JC, Guarda E, Guntaka RV, Weber KT. Regulation of collagen degradation in the rat myocardium after infarction. J Mol Cell Cardiol 1995;27:
Many patients who experience a myocardial infarction
Basic Science Reports Early Short-Term Treatment With Doxycycline Modulates Postinfarction Left Ventricular Remodeling Francisco J. Villarreal, MD, PhD; Michael Griffin, BS; Jeffrey Omens, PhD; Wolfgang
More informationEarly Activation of Metalloproteinases after Experimental Myocardial Infarction Occurs in Infarct and Non-infarct Zones
Early Activation of Metalloproteinases after Experimental Myocardial Infarction Occurs in Infarct and Non-infarct Zones Eyal Herzog, MD, Angu Gu, MD, Takushi Kohmoto, MD, Daniel Burkhoff, MD, and Judith
More informationThe Cardiovascular System and Aging- Is it Built to Fail?
The Cardiovascular System and Aging- Is it Built to Fail? Francis G. Spinale, MD, PhD Professor of Surgery and Cell Biology and Anatomy University of South Carolina School of Medicine Veterans Affairs
More informationNabeel R. Obeid Mentors: Erin A. Booth and Dr. Benedict R. Lucchesi
Cardioprotective Action of Selective Estrogen-receptor Agonists against Myocardial Ischemia and Reperfusion Injury Nabeel R. Obeid Mentors: Erin A. Booth and Dr. Benedict R. Lucchesi Abstract Cell death
More informationEffects of myocardial infarction on catheter defibrillation threshold
Purdue University Purdue e-pubs Weldon School of Biomedical Engineering Faculty Publications Weldon School of Biomedical Engineering 1983 Effects of myocardial infarction on catheter defibrillation threshold
More informationTargeted deletion of MMP-9 attenuates myocardial contractile dysfunction in Heart. Failure. Karni S. Moshal. Walter E. Rodriguez.
Targeted deletion of MMP-9 attenuates myocardial contractile dysfunction in Heart Failure. Karni S. Moshal Walter E. Rodriguez Utpal Sen Suresh C. Tyagi Department of Physiology and Biophysics, University
More informationTargeted Deletion of MMP-9 Attenuates Myocardial Contractile Dysfunction in Heart Failure
Physiol. Res. 57: 379-384, 2008 Targeted Deletion of MMP-9 Attenuates Myocardial Contractile Dysfunction in Heart Failure K. S. MOSHAL, W. E. RODRIGUEZ, U. SEN, S. C. TYAGI Department of Physiology and
More informationTissue repair. (3&4 of 4)
Tissue repair (3&4 of 4) What will we discuss today: Regeneration in tissue repair Scar formation Cutaneous wound healing Pathologic aspects of repair Regeneration in tissue repair Labile tissues rapid
More informationLeft ventricular (LV) remodeling after myocardial infarction
Inhibition of Collagen Synthesis With Prolyl 4-Hydroxylase Inhibitor Improves Left Ventricular Function and Alters the Pattern of Left Ventricular Dilatation After Myocardial Infarction John I. Nwogu,
More informationCorMatrix ECM Bioscaffold
CorMatrix ECM Bioscaffold REMODEL. REGROW. RESTORE. CorMatrix ECM Bioscaffold provides a natural bioscaffold matrix that enables the body s own cells to repair and remodel damaged cardio-vascular tissue.
More informationPercutaneous Mitral Valve Intervention: QuantumCor Device
Percutaneous Mitral Valve Intervention: QuantumCor Device RICHARD R. HEUSER, MD, FACC, FACP, FESC Director Of Cardiology, St. Luke s Medical Center, Phoenix, Arizona Medical Director, Phoenix Heart Center,
More informationIschemic heart disease
Ischemic heart disease Introduction In > 90% of cases: the cause is: reduced coronary blood flow secondary to: obstructive atherosclerotic vascular disease so most of the time it is called: coronary artery
More informationCase Report Multimodality Imaging of Chronic Ischemia
SAGE-Hindawi Access to Research Volume 2011, Article ID 739702, 4 pages doi:10.4061/2011/739702 Case Report Multimodality Imaging of Chronic Ischemia Kiyotake Ishikawa, Dennis Ladage, Kleopatra Rapti,
More informationInflammation in heart failure: biomarker, bystander or mediator
Inflammation in heart failure: biomarker, bystander or mediator Novel matricellular proteins to target Javier Díez, MD, PhD. Centre of Applied Medical Research and University Clinic School of Medicine,
More informationMyocardial Infarction
Myocardial Infarction MI = heart attack Defined as necrosis of heart muscle resulting from ischemia. A very significant cause of death worldwide. of these deaths, 33% -50% die before they can reach the
More informationMesenchymal Stem Cells to Repair Vascular Damage after Chemotherapy: Past, Present and Future
Mesenchymal Stem Cells to Repair Vascular Damage after Chemotherapy: Past, Present and Future Cell Therapy 2014 Las Vegas, NV, USA Sulaiman Al-Hashmi, PhD Sultan Qaboos University Oman What are MSCs? Stem
More informationStratification of heart failure using biomarkers of myocardial fibrosis
Stratification of heart failure using biomarkers of myocardial fibrosis Thesis Master Biology of Disease University of Utrecht Sanne de Jong 0476773 Supervisor: Dr. H.V.M. van Rijen University Medical
More informationCitation Acta medica Nagasakiensia. 1984, 29
NAOSITE: Nagasaki University's Ac Title Author(s) Efficacy of Coenzyme Q10 Administra Aortic Stenosis and Pacemaker Induc Igarashi, Katsuro Citation Acta medica Nagasakiensia. 1984, 29 Issue Date 1984-10-25
More informationBiomarkers in cardiovascular disease. Felix J. Rogers, DO, FACOI April 29, 2018
Biomarkers in cardiovascular disease Felix J. Rogers, DO, FACOI April 29, 2018 Biomarkers NIH: A biomarker is a characteristic that is objectively measured and evaluated as an indicator of normal biological
More informationSupplementary Material
Supplementary Material Induction of myocardial infarction Mice were anesthetized by intraperitoneal injection of pentobarbital (7 mg/kg). In the supine position, endotracheal intubation was performed.
More informationBIOCHEMICAL INVESTIGATIONS IN THE DIAGNOSTICS OF CARDIOVASCULAR DISORDERS. As. MARUSHCHAK M.I.
BIOCHEMICAL INVESTIGATIONS IN THE DIAGNOSTICS OF CARDIOVASCULAR DISORDERS As. MARUSHCHAK M.I. Heart attack symptoms Acute MI Measurement of cardiac enzyme levels Measure cardiac enzyme levels at regular
More informationTopical nanocrystalline silver cream inhibits expression of matrix metalloproteinase-9 in animal models of allergic contact dermatitis.
Topical nanocrystalline silver cream inhibits expression of matrix metalloproteinase-9 in animal models of allergic contact dermatitis. K C Bhol, P J Schechter NUCRYST Pharmaceuticals Inc, Wakefield, MA
More informationImaging of Coronary Artery Disease: II
Acta Radiológica Portuguesa, Vol.XIX, nº 74, pág. 45-51, Abr.-Jun., 2007 Imaging of Coronary Artery Disease: II Jean Jeudy University of Maryland School of Medicine Department of Diagnostic Radiology Armed
More informationAlthough significant extracellular remodeling occurs after
Region- and Type-Specific Induction of Matrix Metalloproteinases in Post Myocardial Infarction Remodeling Eric M. Wilson, BS; Sina L. Moainie, MD; Julia M. Baskin, BA; Abigail S. Lowry, BS; Anne M. Deschamps,
More informationAbout OMICS Group Conferences
About OMICS Group OMICS Group International is an amalgamation of Open Access publications and worldwide international science conferences and events. Established in the year 2007 with the sole aim of
More informationPathophysiology of heart failure with preserved ejection fraction. Extracellular matrix
Pathophysiology of heart failure with preserved ejection fraction Extracellular matrix Javier Díez, MD, PhD. Full Professor of Cardiovascular Medicine and Director Division of Cardiovascular Sciences Centre
More informationCh.15 Cardiovascular System Pgs {15-12} {15-13}
Ch.15 Cardiovascular System Pgs {15-12} {15-13} E. Skeleton of the Heart 1. The skeleton of the heart is composed of rings of dense connective tissue and other masses of connective tissue in the interventricular
More informationUncovering the mechanisms of wound healing and fibrosis
Any Questions??? Ask now or contact support support@sabiosciences.com 1-888-503-3187 International customers: SABio@Qiagen.com Uncovering the mechanisms of wound healing and fibrosis Webinar related questions:
More informationIschaemic Preconditioning prevents the differentiation induced by ischaemia/reperfusion injury of rat cardiac fibroblast to myofibroblast
Ischaemic Preconditioning prevents the differentiation induced by ischaemia/reperfusion injury of rat cardiac fibroblast to myofibroblast Kartika Pertiwi1 and Lisa Chilton2 1: Biology Education Department,
More informationAcute chest pain and ECG need for immediate coronary angiography?
Acute chest pain and ECG need for immediate coronary angiography? Kjell Nikus, MD, PhD Heart Center, Tampere University Hospital, Finland and Samuel Sclarovsky, MD, PhD Tel Aviv University, Israel There
More informationJournal Club Semmler Lorenz
Beer et al. 2015 - Analysis of the Secretome of Apoptotic Peripheral Blood Mononuclear Cells: Impact of Released Proteins and Exosomes for Tissue Regeneration Journal Club 13.11.2017 1 Introduction to
More informationDepartment of Pathology, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts, USA 3
Targeted deletion of matrix metalloproteinase-9 attenuates left ventricular enlargement and collagen accumulation after experimental myocardial infarction Anique Ducharme, 1 Stefan Frantz, 1 Masanori Aikawa,
More informationRecovery of Myocardial Infarction via Unique Modulation of the Cardiac Microenvironment
2016 춘계심혈관통합학술대회, 경주 Recovery of Myocardial Infarction via Unique Modulation of the Cardiac Microenvironment Youngkeun Ahn, MD, PhD Department of Cardiology, Cardiovascular Center Chonnam National University
More informationMammalian Fetal Cardiac Regeneration After Myocardial Infarction Is Associated With Differential Gene Expression Compared With the Adult
Mammalian Fetal Cardiac Regeneration After Myocardial Infarction Is Associated With Differential Gene Expression Compared With the Adult Carlos Zgheib, PhD,* Myron W. Allukian, MD,* Junwang Xu, PhD, Michael
More informationEffect of a nutrient mixture on the localization of extracellular matrix proteins in HeLa human cervical cancer xenografts in female nude mice
Effect of a nutrient mixture on the localization of extracellular matrix proteins in HeLa human cervical cancer xenografts in female nude mice Publication from the Dr. Rath Research Institute Experimental
More informationBEER AND THE HEART: INSIGHTS ON THE EFFECTS ON ALCOHOLIC AND NON-ALCOHOLIC BEER
BEER AND THE HEART: INSIGHTS ON THE EFFECTS ON ALCOHOLIC AND NON-ALCOHOLIC BEER Lina Badimon Cardiovascular Research Center (CRC) CSIC-ICCC Barcelona 7 TH EUROPEAN BEER AND HEALTH SYMPOSIUM BRUSSELS -2014
More informationMimecan and cardiac extracellular matrix integrity Lucas Van Aelst, MD Department of Internal Medicine, University Hospitals Leuven, Leuven, Belgium
Mimecan and cardiac extracellular matrix integrity Lucas Van Aelst, MD Department of Internal Medicine, University Hospitals Leuven, Leuven, Belgium VIB-Vesalius Research Center, KULeuven, Leuven, Belgium
More information1. Cardiomyocytes and nonmyocyte. 2. Extracellular Matrix 3. Vessels שאלה 1. Pathobiology of Heart Failure Molecular and Cellular Mechanism
Pathobiology of Heart Failure Molecular and Cellular Mechanism Jonathan Leor Neufeld Cardiac Research Institute Tel-Aviv University Sheba Medical Center, Tel-Hashomer שאלה 1 התא הנפוץ ביותר (75%~) בלב
More informationc Ischemia (30 min) Reperfusion (8 w) Supplementary Figure bp 300 bp Ischemia (30 min) Reperfusion (4 h) Dox 20 mg/kg i.p.
a Marker Ripk3 +/ 5 bp 3 bp b Ischemia (3 min) Reperfusion (4 h) d 2 mg/kg i.p. 1 w 5 w Sacrifice for IF size A subset for echocardiography and morphological analysis c Ischemia (3 min) Reperfusion (8
More informationTITLE: Epicatechin as a therapeutic strategy to mitigate the development of cardiac remodeling and fibrosis
AWARD NUMBER: W81XWH-16-1-0244 TITLE: Epicatechin as a therapeutic strategy to mitigate the development of cardiac remodeling and fibrosis PRINCIPAL INVESTIGATOR: Francisco Villarreal CONTRACTING ORGANIZATION:
More informationDirect Annuloplasty with QuantumCor: Device Evolution, Techniques and First-in-Man Results
Direct Annuloplasty with QuantumCor: Device Evolution, Techniques and First-in-Man Results RICHARD R. HEUSER, MD, FACC, FACP, FESC, FSCAI Chief of Cardiology, St. Luke s Medical Center, Phoenix, Arizona
More informationEXPERIMENTAL PLEURAL EMPYEMA PATHOLOGIC CHANGES
Trakia Journal of Sciences, Vol. 3, No. 2, pp 61-65, 2005 Copyright 2005 Trakia University Available online at: http://www.uni-sz.bg ISSN 1312-1723 Original Contribution EXPERIMENTAL PLEURAL EMPYEMA PATHOLOGIC
More informationVentricular Interactions in the Normal and Failing Heart
Ventricular Interactions in the Normal and Failing Heart Congenital Cardiac Anesthesia Society 2015 Pressure-volume relations Matched Left ventricle to low hydraulic impedance Maximal stroke work limited
More informationC57BL/6 Mice are More Appropriate. than BALB/C Mice in Inducing Dilated Cardiomyopathy with Short-Term Doxorubicin Treatment
Original Article C57BL/6 Mice are More Appropriate Acta Cardiol Sin 2012;28:236 240 Heart Failure & Cardiomyopathy C57BL/6 Mice are More Appropriate than BALB/C Mice in Inducing Dilated Cardiomyopathy
More informationEFFECT OF INFARCT SIZE LIMITATION BY PROPRANOLOL ON VENTRICULAR ARRHYTHMIAS AFTER MYOCARDIAL INFARCTION
EFFECT OF INFARCT SIZE LIMITATION BY PROPRANOLOL ON VENTRICULAR ARRHYTHMIAS AFTER MYOCARDIAL INFARCTION James R. Stewart,* John K. Gibson,? and Benedict R. Lucchesi t Departments of Internal Medicine *
More informationQuantification of Coronary Arterial Narrowing at Necropsy in Acute Transmural Myocardial Infarction
Quantification of Coronary Arterial Narrowing at Necropsy in Acute Transmural Myocardial Infarction Analysis and Comparison of Findings in 27 Patients and 22 Controls WILLIAM C. ROBERTS, M.D., AND ANCIL
More informationExtracellular matrix Basic and translational science: Highlights of the congress
Extracellular matrix Basic and translational science: Highlights of the congress Stephane Heymans, Maastricht University Medical Centre, CARIM, Netherlands Speaker The extracellular matrix modulates cardiac
More informationCABG alone. It s enough? / Μόνο η αορτοστεφανιαία παράκαμψη είναι αρκετή;
LV Aneurysm and VSD in Ischaemic Heart Failure / Στεφανιαία νόσος, ανεύρυσμα αριστεράς κοιλίας και VSD CABG alone. It s enough? / Μόνο η αορτοστεφανιαία παράκαμψη είναι αρκετή; THEODOROS KARAISKOS CONSULTANT
More informationExercise in Adverse Cardiac Remodeling: of Mice and Men
Exercise in Adverse Cardiac Remodeling: of Mice and Men 17-01-2013 Dirk J Duncker Experimental Cardiology, Cardiology, Thoraxcenter Cardiovascular Research Institute COEUR Erasmus MC, University Medical
More informationMaster Eudipharm 2012 Introductory Module, Principles of Discovery of Medicine and Development Planning. Nathan Mewton, MD, PhD. September 26 th 2012
Master Eudipharm 2012 Introductory Module, Principles of Discovery of Medicine and Development Planning * Nathan Mewton, MD, PhD. September 26 th 2012 *A little bit of History *Rabies a viral disease that
More informationCoagulative Necrosis of Myocardium. Dr Rodney Itaki Division of Pathology
Coagulative Necrosis of Myocardium Dr Rodney Itaki Division of Pathology Coagulative Necrosis Gross pathology: 3 day old infarct: Yellow necrosis surrounded by hyperemic borders. Arrow points to a transmural
More informationDetection and Assessment of MI: Use of Imaging Methods. Robert O. Bonow, M.D.
Detection and Assessment of MI: Use of Imaging Methods Robert O. Bonow, M.D. Detection and Assessment of MI: Use of Imaging Methods Robert O. Bonow, M.D. No Relationships to Disclose Expert Consensus Document
More informationThe Randomized Aldactone Evaluation Study (RALES), a
Limitation of Excessive Extracellular Matrix Turnover May Contribute to Survival Benefit of Spironolactone Therapy in Patients With Congestive Heart Failure Insights From the Randomized Aldactone Evaluation
More informationΒΙΟΔΕΙΚΤΕΣ ΣΤΗΝ ΚΑΡΔΙΑΚΗ ΑΝΕΠΑΡΚΕΙΑ. ΔΗΜΗΤΡΙΟΣ ΤΟΥΣΟΥΛΗΣ Καθηγητής Καρδιολογίας
ΕΘΝΙΚΟ ΚΑΙ ΚΑΠΟΔΙΣΤΡΙΑΚΟ ΠΑΝΕΠΙΣΤΗΜΙΟ ΑΘΗΝΩΝ ΙΑΤΡΙΚΗ ΣΧΟΛΗ Ά ΚΑΡΔΙΟΛΟΓΙΚΗ ΚΛΙΝΙΚΗ Διευθυντής: Καθηγητής Δημήτριος Τούσουλης ΒΙΟΔΕΙΚΤΕΣ ΣΤΗΝ ΚΑΡΔΙΑΚΗ ΑΝΕΠΑΡΚΕΙΑ ΔΗΜΗΤΡΙΟΣ ΤΟΥΣΟΥΛΗΣ Καθηγητής Καρδιολογίας
More informationNuclear Cardiology Pierre-Yves MARIE Department of Nuclear Medicine CHU-Nancy, FRANCE.
Nuclear Cardiology Pierre-Yves MARIE Department of Nuclear Medicine CHU-Nancy, FRANCE. Nuclear Cardiology I - A remaining need of a functional information on myocardial perfusion II - The future: - combining
More informationReperfusion Injury: How Can We Reduce It?
MI/CAD: Practical Question in Management of AMI Patients Reperfusion Injury: How Can We Reduce It? Hyun-Jai Cho, M.D., Ph.D Cardiovascular Center & Department of Internal Medicine Seoul National University
More informationEffect of Short-term Maximal Exercise on BNP Plasma Levels in. Healthy Individuals
1 Effect of Short-term Maximal Exercise on BNP Plasma Levels in Healthy Individuals Jan Krupicka, MD, Tomas Janota, MD, Zdislava Kasalova, MD, Jaromir Hradec, MD 3rd Department of Internal Medicine, 1st
More informationPrevention of sudden cardiac death: With an emphasis on sudden cardiac death from ventricular arrhythmias
Prevention of sudden cardiac death: With an emphasis on sudden cardiac death from ventricular arrhythmias The Toronto ACS Summit Toronto, March 1, 2014 Andrew C.T. Ha, MD, MSc, FRCPC Cardiac Electrophysiology
More informationHealing and Repair. Dr. Nabila Hamdi MD, PhD
Healing and Repair Dr. Nabila Hamdi MD, PhD 1 ILOs Know the classification of human cells according to their ability for proliferation. Understand the mechanism of cellular regeneration. Identify the types
More informationDiagnosis and Management of Acute Myocardial Infarction
Diagnosis and Management of Acute Myocardial Infarction Acute Myocardial Infarction (AMI) occurs as a result of prolonged myocardial ischemia Atherosclerosis leads to endothelial rupture or erosion that
More informationAcute coronary syndrome. Dr LM Murray Chemical Pathology Block SA
Acute coronary syndrome Dr LM Murray Chemical Pathology Block SA13-2014 Acute myocardial infarction (MI) MI is still the leading cause of death in many countries It is characterized by severe chest pain,
More informationRegenerative Tissue Matrix in Treatment of Wounds
Regenerative Tissue Matrix in Treatment of Wounds Learning Objectives Differentiate between reparative and regenerative healing Review surgical techniques for applying a regenerative tissue scaffold to
More informationHistopathology: healing
Histopathology: healing These presentations are to help you identify, and to test yourself on identifying, basic histopathological features. They do not contain the additional factual information that
More informationMyocardial injury, necrosis and infarction
Myocardial injury, necrosis and infarction Harvey White Green Lane Cardiovascular Service and Cardiovascular Research Unit Auckland City Hospital, Auckland, New Zealand Faculty Disclosure In accordance
More informationKeeping the Small Aortic Aneurysm Small
Keeping the Small Aortic Aneurysm Small John A. Curci, MD, FACS Associate Professor of Vascular and Endovascular Surgery Director, Aortic Aneurysm Research Laboratories, Washington University Principal
More informationTITLE: Breast Tumor-Generated Type 1 Collagen Breakdown Fragments Act as Matrikines to Drive Osteolysis
AD Award Number: W81XWH-08-1-0639 TITLE: Breast Tumor-Generated Type 1 Collagen Breakdown Fragments Act as Matrikines to Drive Osteolysis PRINCIPAL INVESTIGATOR: Ching Hua William Wu PhD. CONTRACTING ORGANIZATION:
More informationCardioprotection by endogenous fibroblast growth factor 2 in cardiac ischemia-reperfusion injury in vivo
Washington University School of Medicine Digital Commons@Becker Conference Abstracts and Posters Division of Emergency Medicine/Emergency Care Research Section 2011 Cardioprotection by endogenous fibroblast
More informationשינויים מולקולאריים ומבניים באי ספיקת לב אפשרויות לטיפול עתידני
שינויים מולקולאריים ומבניים באי ספיקת לב אפשרויות לטיפול עתידני פרופ יהונתן ליאור 1 Braunwald s Heart Disease 8th Edition Chapter 21 Mechanisms of Cardiac Contraction and Relaxation Chapter 22 Pathophysiology
More informationCase Report. Case Report. Ana Lúcia Martins Arruda, Altamiro Ozório, Eloisa Mattos, José Lázaro de Andrade, Thomas Porter, Wilson Mathias Jr
Case Report Hypoperfusion of the Left Ventricle in the Absence of Changes in Segmental Contractility as Observed through Echocardiography by Using Microbubbles During Dobutamine Infusion Ana Lúcia Martins
More informationSupplementary Figure 1. Characterization of NMuMG-ErbB2 and NIC breast cancer cells expressing shrnas targeting LPP. NMuMG-ErbB2 cells (a) and NIC
Supplementary Figure 1. Characterization of NMuMG-ErbB2 and NIC breast cancer cells expressing shrnas targeting LPP. NMuMG-ErbB2 cells (a) and NIC cells (b) were engineered to stably express either a LucA-shRNA
More informationZamaneh Kassiri, PhD Associate Professor Department of Physiology University of Alberta. May 27, 2016
Zamaneh Kassiri, PhD Associate Professor Department of Physiology University of Alberta May 27, 2016 Fluorescent microscope PSR staining/confocal microscopy Electron microscope Scanning electron microscopy
More informationRationale for Prophylactic Support During Percutaneous Coronary Intervention
Rationale for Prophylactic Support During Percutaneous Coronary Intervention Navin K. Kapur, MD, FACC, FSCAI Assistant Director, Interventional Cardiology Director, Interventional Research Laboratories
More informationPresenter Disclosure Information
Various Morphological Types of Ventricular Premature Beats with Fragmented QRS Waves on 12 Lead Holter ECG had a Positive Relationship with Left Ventricular Fibrosis on CT in Patients with Hypertrophic
More informationIn the name of GOD. Animal models of cardiovascular diseases: myocardial infarction & hypertension
In the name of GOD Animal models of cardiovascular diseases: myocardial infarction & hypertension 44 Presentation outline: Cardiovascular diseases Acute myocardial infarction Animal models for myocardial
More informationRegulation of Myocardial Matrix Metalloproteinase Expression and Activity by Cardiac Fibroblasts
IUBMB Life, 64(2): 143 150, February 2012 Critical Review Regulation of Myocardial Matrix Metalloproteinase Expression and Activity by Cardiac Fibroblasts Neil A. Turner and Karen E. Porter Division of
More informationDr. Khairy Abdel Dayem. Professor of Cardiology Ain-Shams University
Dr. Khairy Abdel Dayem Professor of Cardiology Ain-Shams University RALES Randomized Aldactone Evaluation Study 1. NEJM 1999 2. Bertram Pitt 3. 1660 Class III and IV HF patients 4. EF 35% 5. 841 placebo
More informationNURSING DEPARTMENT CRITICAL CARE POLICY MANUAL CRITICAL CARE PROTOCOLS. ACTIVASE (t-pa) INFUSION PROTOCOL FOR ACUTE MYOCARDIAL INFARCTION
NURSING DEPARTMENT CRITICAL CARE POLICY MANUAL CRITICAL CARE PROTOCOLS ACTIVASE (t-pa) FOR ACUTE MYOCARDIAL INFARCTION I. PURPOSE: A. To reduce the extent of myocardial infarction by lysing the clot in
More information1) Severe, crushing substernal chest pain 2) radiate to the neck, jaw, epigastrium, or left arm. 3- rapid and weak pulse 4- nausea (posterior MI).
1) Severe, crushing substernal chest pain 2) radiate to the neck, jaw, epigastrium, or left arm. 3- rapid and weak pulse 4- nausea (posterior MI). 5- cardiogenic shock (massive MIs >40% of the left ventricle)
More informationPost Operative Troponin Leak: David Smyth Christchurch New Zealand
Post Operative Troponin Leak: Does It Really Matter? David Smyth Christchurch New Zealand Life Was Simple Once Transmural Infarction Subendocardial Infarction But the Blood Tests Were n t Perfect Creatine
More informationStretching Cardiac Myocytes: A Finite Element Model of Cardiac Tissue
Megan McCain ES240 FEM Final Project December 19, 2006 Stretching Cardiac Myocytes: A Finite Element Model of Cardiac Tissue Cardiac myocytes are the cells that constitute the working muscle of the heart.
More informationLe FDG dans l évaluation de la viabilité : Quelle place par rapport aux autres traceurs?
Le FDG dans l évaluation de la viabilité : Quelle place par rapport aux autres traceurs? Pierre-Yves MARIE, Médecine Nucléaire, CHU de Nancy PET Gated-SPECT MRI FDG imaging: effect of dietary status fasting
More informationCardiac Pathology 2: Heart Failure, Ischemic Heart Disease and other assorted stuff. Kris=ne Kra>s, M.D.
Cardiac Pathology 2: Heart Failure, Ischemic Heart Disease and other assorted stuff Kris=ne Kra>s, M.D. Cardiac Pathology Outline Blood Vessels Heart I Heart II Cardiac Pathology Outline Blood Vessels
More informationDirect Renin Inhibitor Attenuates Left Ventricular Remodeling in Post-Myocardial Infarction Heart Failure Mice
Original Article Acta Cardiol Sin 2013;29:160 167 Heart Failure Direct Renin Inhibitor Attenuates Left Ventricular Remodeling in Post-Myocardial Infarction Heart Failure Mice Ning-I Yang, Chia-Chi Liao,
More informationPretargeting and Bioorthogonal Click Chemistry-Mediated Endogenous Stem Cell Homing for Heart Repair
Pretargeting and Bioorthogonal Click Chemistry-Mediated Endogenous Stem Cell Homing for Heart Repair Mouse Model of Myocardial Infarction (MI) All animal work was compliant with the Institutional Animal
More informationMYOCARDIAL INFARCTION AND PREPONDERANCE OF A VENTRICLE
POTASSIUM EFFECTS ON T WAVE INVERSION IN MYOCARDIAL INFARCTION AND PREPONDERANCE OF A VENTRICLE BY E. P. SHARPEY-SCHAFER From the Department of Medicine, British Postgraduate Medical School, London Received
More informationAP2 Lab 3 Coronary Vessels, Valves, Sounds, and Dissection
AP2 Lab 3 Coronary Vessels, Valves, Sounds, and Dissection Project 1 - BLOOD Supply to the Myocardium (Figs. 18.5 &18.10) The myocardium is not nourished by the blood while it is being pumped through the
More informationDICHIARAZIONE Relatore: NADIA PASINETTI
DICHIARAZIONE Relatore: NADIA PASINETTI Come da nuova regolamentazione della Commissione Nazionale per la Formazione Continua del Ministero della Salute, è richiesta la trasparenza delle fonti di finanziamento
More information3/27/2014. Introduction.
Introduction. Myocardial perfusion & contractility becomes abnormal immediately after the onset of ischaemia, even before the development of the symptoms & ST segment changes. 1 Myocardial Wall Motion
More informationCase Presentation Conference Ravi Dhanisetty, M.D. Kings County Hospital Center
Case Presentation Morbidity and Mortality Conference Ravi Dhanisetty, M.D. Kings County Hospital Center 1 May 2009 Case Presentation 53 year old male bus driver had a syncopal episode and found down unresponsive.
More informationGinkgo biloba extract postconditioning reduces myocardial ischemia reperfusion injury
Ginkgo biloba extract postconditioning reduces myocardial ischemia reperfusion injury K. Ran 1, D.-L. Yang 1, Y.-T. Chang 1, K.-M. Duan 2, Y.-W. Ou 2, H.-P. Wang 3 and Z.-J. Li 1 1 Department of Anesthesiology,
More informationThe role of Neutrophil Gelatinase Associated Lipocalin in linking Depression and Heart Failure.
The role of Neutrophil Gelatinase Associated Lipocalin in linking Depression and Heart Failure. Leonie Gouweleeuw 1, Uli LM Eisel 1,2, Pieter JW Naude 1, Regien G. Schoemaker 1,3 1 : Department of Molecular
More informationObjectives. Acute Coronary Syndromes; The Nuts and Bolts. Overview. Quick quiz.. How dose the plaque start?
Objectives Acute Coronary Syndromes; The Nuts and Bolts Michael P. Gulseth, Pharm. D., BCPS Pharmacotherapy II Spring 2006 Compare and contrast pathophysiology of unstable angina (UA), non-st segment elevation
More informationSUPPLEMENTARY INFORMATION
doi:10.1038/nature10188 Supplementary Figure 1. Embryonic epicardial genes are down-regulated from midgestation stages and barely detectable post-natally. Real time qrt-pcr revealed a significant down-regulation
More informationFurther Studies on the Effect of Arteriovenous Fistulas and Elevations of Sinus Pressure
Further Studies on the Effect of Arteriovenous Fistulas and Elevations of Sinus Pressure on Mortality Rates Following Acute Coronary Occlusions By GEORGE SMITH, F.R.C.S., JAMES DEMMING, MORTON ELEFF, AND
More informationHealing & Repair. Tissue Regeneration
Healing & Repair Dr. Srikumar Chakravarthi Repair & Healing: Are they same? Repair :Regeneration of injured cells by cells of same type, as with regeneration of skin/oral mucosa (requires basement membrane)
More informationImprovement in collagen metabolism after 12 weeks cardiac resynchronization therapy in patients with ischaemic cardiomyopathy
Research Report Improvement in collagen metabolism after 12 weeks cardiac resynchronization therapy in patients with ischaemic cardiomyopathy Journal of International Medical Research 41(1) 200 207! The
More informationAnatomy of the Heart
Biology 212: Anatomy and Physiology II Anatomy of the Heart References: Saladin, KS: Anatomy and Physiology, The Unity of Form and Function 8 th (2018). Required reading before beginning this lab: Chapter
More informationTranscatheter Closure of Acute Myocardial Infarction VSD
The 10 th Anniversary, Interventional Vascular Therapeutics ANGIOPLASTY SUMMIT 2005 TCT ASIA PACIFIC Transcatheter Closure of Acute Myocardial Infarction VSD Dr. Mullasari S Ajit Senior Consultant Cardiologist
More informationRole of matrix metalloproteinase-9 in endothelial apoptosis in chronic heart failure in mice
J Appl Physiol 99: 2398 2405, 2005. First published August 4, 2005; doi:10.1152/japplphysiol.00442.2005. Role of matrix metalloproteinase-9 in endothelial apoptosis in chronic heart failure in mice Alexander
More information