Cardiovascular Division, Brigham and Women s Hospital, Harvard Medical School

Size: px
Start display at page:

Download "Cardiovascular Division, Brigham and Women s Hospital, Harvard Medical School"

Transcription

1 Low Endothelial Shear Stress Upregulates Atherogenic and Inflammatory Genes Extremely Early in the Natural History of Coronary Artery Disease in Diabetic Hyperlipidemic Juvenile Swine Michail I. Papafaklis, Konstantinos C. Koskinas, Aaron B. Baker, Yiannis S. Chatzizisis, Ahmet U. Coskun, Joseph W. Franses, Saeko Takahashi, Elazer R. Edelman, Peter H. Stone, Charles L. Feldman Cardiovascular Division, Brigham and Women s Hospital, Harvard Medical School Harvard-MIT Division of Health Sciences, Massachusetts Institute of Technology

2 Disclosure Statement Conflicts of Interest Nothing to disclose

3 The Local Hemodynamic Environment is a Critical Factor in the Natural History of Atherosclerosis Although atherosclerosis is a systemic disease, its distribution is multifocal and heterogeneous Malek, et al. JAMA 1999;282: Local hemodynamic factors exhibit remarkable heterogeneity over short distances and are responsible for the heterogeneity in the spatial distribution of atherosclerotic lesions Understanding the molecular mechanisms related to initiation of atherosclerosis and the individual natural history of early lesions in vivo will allow for identification of areas at highest risk and selective preemptive therapy to reduce adverse cardiac events Papafaklis MI, et al. Curr Opin Cardiol 2010;25:627-38

4 Endothelial Shear Stress (ESS) Exerts a Multifactorial Influence on the Arterial Wall In vitro studies demonstrated that ESS determines regional cell phenotypes promoting atherosclerosis susceptibility or atherosclerosis protection García-Cardeña G, et al. Ann N Y Acad Sci 2001;947:1-6 Davies PF. Nat Clin Pract Cardiovasc Med 2009; 6:16-26 The presence of disturbed flow (low/oscillatory ESS) tips the balance of gene expression towards atherosclerosis susceptibility Hajra L, et al. Proc Natl Acad Sci USA 2000;97: In vitro experiments (cell cultures) are limited by the artificial application of flow conditions without accounting for the complex nature of the arterial environment Available in vivo studies primarily in mouse aortas are limited by the large differences in ESS levels compared to humans Suo J, et al. Arterioscler Thromb Vasc Biol 2007;27: The in vivo effect of local ESS on the cellular mechanisms responsible for coronary atherosclerosis initiation and early lesion formation has not been studied

5 Study Objectives To investigate the in vivo role of local ESS early in the natural history of coronary atherosclerosis, and assess the molecular mechanisms that link low ESS with the formation of early lesions, utilizing a pig model of human-like atherosclerosis To test the hypothesis that low ESS in vivo Upregulates pro-inflammatory and pro-atherogenic signaling pathways Augments the expression of leukocyte adhesion molecules and chemokines Promotes the uptake and catabolism of oxidized LDL reinforcing a pro-inflammatory vicious cycle

6 Methods: Study Protocol 4 Male Yorkshire Swine (Age: 3 months old) 11 coronary arteries Week 0 Week 4 Baseline Week 8 Follow-up Induction of Diabetes (IV streptozotocin) Initiation of High-fat Diet In Vivo Vascular Profiling Coronary Angiography, IVUS & Computational Fluid Dynamics Sacrifice Molecular Biology Analyses & Histopathology

7 Methods: Vascular Profiling for Serial, In Vivo Measurement of Local ESS and Wall Morphology Coronary Angiography Intravascular Ultrasound Coronary Blood Flow Acquisition of Image Data 3D Reconstruction of Lumen and EEM Generation of Grid for Computational Fluid Dynamics Determination of Velocity Vectors and Shear Stress Numerical Computation Stone PH, et al. Circulation 2003;108:

8 Circumference Circumference Methods: Identification of Arterial Segments in the Harvested Coronary Arteries Low Low High Baseline ESS Follow-up ESS 0 o 180 o 360 o 0 o 180 o Side branch Side branches [Pa] 3-mm segments of interest were identified: Baseline Low ESS ( 1.2 Pa; n=21) Baseline Higher ESS (>1.2 Pa; n=24) 360 o Side branch Side branches Axial Length [mm] Side branches were identified on the arteries harvested at follow-up The exact location of each segment of interest was identified on the preserved coronary arteries

9 Methods Molecular Biology & Histopathologic Analyses GENE EXPRESSION mrna was isolated from the intima and media of cryosections of the arterial segments Real Time RT-PCR for mrna expression of: Transcription Factors: NFκB1, KLF-2 Leukocyte Adhesion Molecules: ICAM-1, VCAM-1 Chemokines and Molecules Related to the Inflammatory Pathway: MCP-1, HMOX-1 Oxidized LDL Uptake and Catabolism: OxLDL receptor (LOX-1), Lp-PLA 2 HISTOPATHOLOGY MCP-1 Immunofluorescence for chemokine protein expression CD45 Immunostaining/Immunofluorescence for inflammatory cells

10 Results: Endothelial Shear Stress Regulates Critical Signaling Pathways Nuclear Factor kappa B1 LOW ESS Krüppel-like Factor-2 Induces Inflammatory Processes Downregulates Atheroprotection ATHEROGENESIS Atherogenesis Atheroprotection

11 Results: Low ESS Upregulates the Expression of Intercellular Adhesion Molecule-1 Upregulation of ICAM-1 leads to increased adhesion of inflammatory cells on the endothelial surface VCAM-1: vascular cell adhesion molecule-1

12 Results: Dose-Response Relationship Between ESS Magnitude and MCP-1 Gene Expression Expression of Monocyte Chemoattractant Protein-1 leads to increased monocyte penetration into the intima MCP-1 mrna= Ln(ESS) r =0.63 p<0.01 MCP-1

13 Results: Augmented MCP-1 Protein Expression in Regions Exposed to Low ESS MCP-1 Low ESS Lumen Higher ESS Lumen CD45 Lumen Media Intima MCP-1 Intima Media Lumen Intima Intima merge Lumen Media CD45 Media Lumen Media Intima Co-localization of MCP-1 expression with dense inflammatory infiltration Media Intima merge Minimal MCP-1 expression and reduced inflammatory infiltration

14 Results: Low ESS is Associated with Early Upregulation of LOX-1 and Lp-PLA 2 Lectin-like Oxidized LDL receptor-1 LOX-1 OxLDL binding, internalization and degradation in ECs Promotes EC activation Lp-PLA 2 Cleaves the oxidized PC to lysopc & oxidized free fatty acids Lipoprotein associated Phospholipase A 2 LysoPC: Lyso-PhosphatidylCholine

15 Results: Increased Expression of Heme Oxygenase-1 in Coronary Segments with Low ESS Inflammatory Signaling Related Pathway HMOX-1 is expressed in the lesion as a compensatory mechanism Oxidative Stress HMOX-1

16 Results: Low ESS Regions Exhibit Early Increase in Inflammatory Cell Infiltration CD45 Low ESS CD45 Higher ESS M M M M CD45 CD45 M: media intima-media border (internal elastic lamina)

17 Summary The Effect of Low ESS on Endothelial Cell Processes Drives the Focal Development of Inflammation and Leads to Early Atherosclerotic Lesions Low ESS Up-regulation of pro-inflammatory pathways Down-regulation of atheroprotective pathways Endothelial Cell Activation Increased OxLDL Uptake Increased Leukocyte Adhesion Augmented Leukocyte Penetration Increased OxLDL Catabolism Inflammation Early Lesion Formation

18 Conclusions Coronary regions of low ESS exhibit endothelial activation and inflammatory infiltration extremely early in the natural history of coronary artery disease Low ESS increased the expression of multiple atherogenic molecules within only 8 weeks following diabetes/hypercholesterolemia induction in juvenile swine Augmented expression of leukocyte adhesion molecules and increased leukocyte penetration into the intima co-localizing with dense inflammatory infiltration Increased oxidized LDL uptake and catabolism to pro-inflammatory compounds (i.e., LysoPC and oxidized fatty acids), all of which reinforce endothelial cell activation and the inflammatory response In vivo assessment of local ESS may identify early arterial regions prone to lesion formation and is suitable for surveillance of atherogenesis opportunities for preemptive treatments (local drug delivery?) to reduce the atherosclerotic burden and prevent adverse cardiac events

19 Acknowledgements Brigham and Women s Hospital Harvard Medical School Vascular Profiling Lab Peter H. Stone, MD Charles L. Feldman, ScD Konstantinos C. Koskinas, MD, MSc Yiannis S. Chatzizisis, MD, PhD Saeko Takahashi, MD Antonios A. Antoniadis, MD, PhD Libby Lab Peter Libby, MD Galina K. Sukhova, PhD Harvard-MIT Division of Health Sciences & Technology Edelman Lab Elazer R. Edelman, MD, PhD Aaron B. Baker, PhD Michael Jonas, MD Northeastern University Mechanical and Industrial Engineering Ahmet U. Coskun, PhD University of Washington Charles Maynard, PhD Funding Sources George D. Behrakis Research Fellowship Hellenic Heart Foundation Hellenic Harvard Foundation Boston Scientific Inc. Novartis Pharmaceuticals Inc.

Ανάπτυξης Ευάλωτων Αθηρωματικών Πλακών

Ανάπτυξης Ευάλωτων Αθηρωματικών Πλακών Σεμινάριο Ομάδων Εργασίας Ελληνική Καρδιολογική Εταιρεία 17-19 Φεβρουαρίου 2011 Shear Stress και Νέοι Μοριακοί Μηχανισμοί Ανάπτυξης Ευάλωτων Αθηρωματικών Πλακών Γιάννης Χατζηζήσης, MD, PhD, FAHA, FESC

More information

Coronary Heart Disease

Coronary Heart Disease Coronary Heart Disease Natural History of Experimental Coronary Atherosclerosis and Vascular Remodeling in Relation to Endothelial Shear Stress A Serial, In Vivo Intravascular Ultrasound Study Konstantinos

More information

LIPOPROTEIN-ASSOCIATED PHOSPHOLIPASE A 2 : EFFECTS OF LOW DENSITY LIPOPROTEIN APHERESIS

LIPOPROTEIN-ASSOCIATED PHOSPHOLIPASE A 2 : EFFECTS OF LOW DENSITY LIPOPROTEIN APHERESIS LIPOPROTEIN-ASSOCIATED PHOSPHOLIPASE A 2 : EFFECTS OF LOW DENSITY LIPOPROTEIN APHERESIS Patrick M. Moriarty, M.D., FACP, Director, Atherosclerosis and LDL-Apheresis Center, University of Kansas Medical

More information

Definitions of ESS and Blood Flow Patterns

Definitions of ESS and Blood Flow Patterns Journal of the American College of Cardiology Vol. 49, No. 25, 2007 2007 by the American College of Cardiology Foundation ISSN 0735-1097/07/$32.00 Published by Elsevier Inc. doi:10.1016/j.jacc.2007.02.059

More information

Although advanced plaques that rupture and trigger most

Although advanced plaques that rupture and trigger most Thin-Capped Atheromata With Reduced Collagen Content in Pigs Develop in Coronary Arterial Regions Exposed to Persistently Low Endothelial Shear Stress Konstantinos C. Koskinas,* Galina K. Sukhova,* Aaron

More information

Effects of a dietary intervention to reduce saturated fat on markers of inflammation and cardiovascular disease.

Effects of a dietary intervention to reduce saturated fat on markers of inflammation and cardiovascular disease. Michael Garshick, MD PGY-1 Columbia University Medical Center Effects of a dietary intervention to reduce saturated fat on markers of inflammation and cardiovascular disease. Study Purpose and Rationale:

More information

Inflammation: Novel Target for Cardiovascular Risk Reduction

Inflammation: Novel Target for Cardiovascular Risk Reduction Inflammation: Novel Target for Cardiovascular Risk Reduction Andrew Zalewski, M.D. Thomas Jefferson University, Philadelphia GlaxoSmithKline, Philadelphia Why inflammation? Population-based studies: low

More information

The New Gold Standard for Lipoprotein Analysis. Advanced Testing for Cardiovascular Risk

The New Gold Standard for Lipoprotein Analysis. Advanced Testing for Cardiovascular Risk The New Gold Standard for Lipoprotein Analysis Advanced Testing for Cardiovascular Risk Evolution of Lipoprotein Testing The Lipid Panel Total Cholesterol = VLDL + LDL + HDL Evolution of Lipoprotein Testing

More information

The 10 th International & 15 th National Congress on Quality Improvement in Clinical Laboratories

The 10 th International & 15 th National Congress on Quality Improvement in Clinical Laboratories The 10 th International & 15 th National Congress on Quality Improvement in Clinical Laboratories Cardiac biomarkers in atherosclerosis Najma Asadi MD-APCP Ross and Colleagues in 1973: Response to Injury

More information

Metabolism and Atherogenic Properties of LDL

Metabolism and Atherogenic Properties of LDL Metabolism and Atherogenic Properties of LDL Manfredi Rizzo, MD, PhD Associate Professor of Internal Medicine Faculty of Medicine, University of Palermo, Italy & Affiliate Associate Professor of Internal

More information

Innate Immunity in Atherosclerosis

Innate Immunity in Atherosclerosis Innate Immunity in Atherosclerosis Peter Libby Brigham & Women s Hospital Harvard Medical School IAS Amsterdam May 26, 2015 ACS Stable demand angina Characteristics of Atherosclerotic Plaques Associated

More information

Inflammation plays a major role in atherosclerosis, 1 and

Inflammation plays a major role in atherosclerosis, 1 and Soluble P-Selectin and the Risk of Future Cardiovascular Events Paul M. Ridker, MD; Julie E. Buring, ScD; Nader Rifai, PhD Background P-selectin, a cell-surface adhesion molecule involved in leukocyte

More information

Future Applications of Contrast Echocardiography

Future Applications of Contrast Echocardiography Future Applications of Contrast Echocardiography Jonathan R. Lindner, M.D. Knight Cardiovascular Institute Oregon Health & Science University Portland, Oregon, USA Disclosures: Investigator-initiated grant

More information

Roles of Flow Mechanics in Vascular Cell Biology in Health and Disease

Roles of Flow Mechanics in Vascular Cell Biology in Health and Disease Roles of Flow Mechanics in Vascular Cell Biology in Health and Disease Shu Chien Dept. of Bioengineering & Medicine UC, San Diego Presented by Ming-Shaung Ju Dept. of Mech. Eng., NCKU, Tainan Background

More information

and Restenosis Yangsoo Jang, MD, PhD. Yonsei University College of Medicine

and Restenosis Yangsoo Jang, MD, PhD. Yonsei University College of Medicine PPAR- Agonist and In-Stent Restenosis Yangsoo Jang, MD, PhD. Yonsei University College of Medicine Peroxisome Proliferator- activated Receptors (PPAR) Lipid-activated transcription factors : => regulating

More information

Role of apolipoprotein B-containing lipoproteins in the development of atherosclerosis Jan Borén MD, PhD

Role of apolipoprotein B-containing lipoproteins in the development of atherosclerosis Jan Borén MD, PhD Role of apolipoprotein B-containing lipoproteins in the development of atherosclerosis Jan Borén MD, PhD Our laboratory focuses on the role of apolipoprotein (apo) B- containing lipoproteins in normal

More information

THE ROLE OF THE NFκB PATHWAY IN ATHEROSCLEROSIS

THE ROLE OF THE NFκB PATHWAY IN ATHEROSCLEROSIS THE ROLE OF THE NFκB PATHWAY IN ATHEROSCLEROSIS Claudia Monaco, Jennifer Grosjean, and Ewa Paleolog, Kennedy Institute of Rheumatology & Division of Surgery, Anaesthetics and Intensive Care, Faculty of

More information

Arteriosclerosis & Atherosclerosis

Arteriosclerosis & Atherosclerosis Arteriosclerosis & Atherosclerosis Arteriosclerosis = hardening of arteries = arterial wall thickening + loss of elasticity 3 types: -Arteriolosclerosis -Monckeberg medial sclerosis -Atherosclerosis Arteriosclerosis,

More information

Adipose Tissue as an Endocrine Organ. Abdel Moniem Ibrahim, MD Professor of Physiology Cairo University

Adipose Tissue as an Endocrine Organ. Abdel Moniem Ibrahim, MD Professor of Physiology Cairo University Adipose Tissue as an Endocrine Organ Abdel Moniem Ibrahim, MD Professor of Physiology Cairo University Functions of Adipose Tissue Adipose tissue expresses and secretes a variety of bioactive peptides,

More information

Child born in year /3 will die before parents in US (diabetes)

Child born in year /3 will die before parents in US (diabetes) Child born in year 2000-1/3 will die before parents in US (diabetes) ATP III identified 6 components of the metabolic syndrome that relate to CVD 1. Abdominal obesity 2. Atherogenic dyslipidemia (elevated

More information

Lipid/Lipoprotein Structure and Metabolism (Overview)

Lipid/Lipoprotein Structure and Metabolism (Overview) Lipid/Lipoprotein Structure and Metabolism (Overview) Philip Barter President, International Atherosclerosis Society Centre for Vascular Research University of New South Wales Sydney, Australia Disclosures

More information

III. Results and Discussion

III. Results and Discussion III. Results and Discussion 1. Histological findings in the coronary artery Twenty-four swine had surgical treatments performed in two of the coronary arteries, LAD as well as either the LCX or RCA. A

More information

FFR CT : Beyond FFR. Bon-Kwon Koo, MD, PhD. Seoul National University Hospital, Seoul, Korea. Seoul National University Hospital Cardiovascular Center

FFR CT : Beyond FFR. Bon-Kwon Koo, MD, PhD. Seoul National University Hospital, Seoul, Korea. Seoul National University Hospital Cardiovascular Center FFR CT : Beyond FFR Bon-Kwon Koo, MD, PhD, Seoul, Korea Patient-specific non-invasive coronary hemodynamic assessment Non-invasive, Pt-specific Hemodynamics Pressure Pressure difference Pressure gradient

More information

PPAR history of research

PPAR history of research PPAR Rubens, 1640 PPAR history of research number of publications 3000 2000 1000 0 till now: : 16 296 publications 1985 1990 1995 2000 2005 year liver, brown adipocytes, kidney, heart, skeletal muscles,

More information

10/17/16. Assessing cardiovascular risk through use of inflammation testing

10/17/16. Assessing cardiovascular risk through use of inflammation testing Assessing cardiovascular risk through use of inflammation testing Anthony L. Lyssy, DO Medical Director and Managing Partner Diamond Physicians Dallas, TX Response to Injury Hypothesis Injury Response

More information

Stewart et al. CD36 ligands promote sterile inflammation through assembly of a TLR 4 and 6 heterodimer

Stewart et al. CD36 ligands promote sterile inflammation through assembly of a TLR 4 and 6 heterodimer NFκB (fold induction) Stewart et al. ligands promote sterile inflammation through assembly of a TLR 4 and 6 heterodimer a. mrna (fold induction) 5 4 3 2 1 LDL oxldl Gro1a MIP-2 RANTES mrna (fold induction)

More information

Tracking a Killer Molecule

Tracking a Killer Molecule Tracking a Killer Molecule Mercodia Oxidized LDL ELISA www.mercodia.com Mercodia Oxidized LDL ELISA products Product Catalog No Kit size Oxidized LDL ELISA 10-1143-01 96 wells Oxidized LDL competitive

More information

Pathology of Coronary Artery Disease

Pathology of Coronary Artery Disease Pathology of Coronary Artery Disease Seth J. Kligerman, MD Pathology of Coronary Artery Disease Seth Kligerman, MD Assistant Professor Medical Director of MRI University of Maryland Department of Radiology

More information

Addressing Vascular Plaque Ruptures

Addressing Vascular Plaque Ruptures Transcript Details This is a transcript of an educational program accessible on the ReachMD network. Details about the program and additional media formats for the program are accessible by visiting: https://reachmd.com/programs/medical-breakthroughs-from-penn-medicine/addressing-vascularplaque-ruptures/3131/

More information

USING NON -TRADITIONAL RISK MARKERS IN ASSESSING CV RISK

USING NON -TRADITIONAL RISK MARKERS IN ASSESSING CV RISK USING NON -TRADITIONAL RISK MARKERS IN ASSESSING CV RISK JAMES M FALKO MD PROFESSOR OF MEDICINE UNIVERSITY OF COLORADO Adapted from: Rader D. N Engl J Med. 2000 hs-crp (mg/l) 6 5 4 3 2 1 *p

More information

Coronary Heart Disease

Coronary Heart Disease Coronary Heart Disease Prediction of Progression of Coronary Artery Disease and Clinical Outcomes Using Vascular Profiling of Endothelial Shear Stress and Arterial Plaque Characteristics The PREDICTION

More information

Summary and concluding remarks

Summary and concluding remarks Summary and concluding remarks This thesis is focused on the role and interaction of different cholesterol and phospholipid transporters. Cholesterol homeostasis is accomplished via a tightly regulated

More information

Treatment of lesions at bifurcations: General perspective

Treatment of lesions at bifurcations: General perspective ESC Congress 2011 27-31 August, Paris, France Treatment of lesions at bifurcations: General perspective Goran Stankovic MD, PhD, FESC Division of Cardiology Clinical Center of Serbia, Belgrade Serbia Potential

More information

High density lipoprotein metabolism

High density lipoprotein metabolism High density lipoprotein metabolism Lipoprotein classes and atherosclerosis Chylomicrons, VLDL, and their catabolic remnants Pro-atherogenic LDL HDL Anti-atherogenic Plasma lipid transport Liver VLDL FC

More information

Thematic review series: The Immune System and Atherogenesis

Thematic review series: The Immune System and Atherogenesis thematic review Thematic review series: The Immune System and Atherogenesis Lipoprotein-associated inflammatory proteins: markers or mediators of cardiovascular disease? Alan Chait, 1 Chang Yeop Han, John

More information

Dyslipidemia Endothelial dysfunction Free radicals Immunologic

Dyslipidemia Endothelial dysfunction Free radicals Immunologic ATHEROSCLEROSIS Hossein Mehrani Professor of Clinical Biochemistry Definition Atherosclerosis: Is a chronic inflammatory process characterized by plaque formation within the vessel wall of arteries and

More information

Left main coronary artery (LMCA): The proximal segment

Left main coronary artery (LMCA): The proximal segment Anatomy and Pathology of Left main coronary artery G Nakazawa Tokai Univ. Kanagawa, Japan 1 Anatomy Difinition Left main coronary artery (LMCA): The proximal segment RCA AV LAD LM LCX of the left coronary

More information

NAM JUNE PAIK: Rhapsody in Video

NAM JUNE PAIK: Rhapsody in Video NAM JUNE PAIK: Rhapsody in Video 혈관연구회추계학회 2007.10.13 Renin-angiotensin-aldosterone System Kwang Kon Koh, MD, FACC, FAHA Cardiology Gachon University Gil Medical Center Incheon, Korea Cytokines oxldl Ang

More information

The apolipoprotein story

The apolipoprotein story Atherosclerosis Supplements 7 (2006) 23 27 The apolipoprotein story Frank M. Sacks a,b, a Department of Nutrition, Harvard School of Public Health, Boston, MA, USA b Department of Medicine, Harvard Medical

More information

renoprotection therapy goals 208, 209

renoprotection therapy goals 208, 209 Subject Index Aldosterone, plasminogen activator inhibitor-1 induction 163, 164, 168 Aminopeptidases angiotensin II processing 64 66, 214 diabetic expression 214, 215 Angiotensin I intrarenal compartmentalization

More information

Imaging Atheroma The quest for the Vulnerable Plaque

Imaging Atheroma The quest for the Vulnerable Plaque Imaging Atheroma The quest for the Vulnerable Plaque P.J. de Feijter 1. Department of Cardiology 2. Department of Radiology Coronary Heart Disease Remains the Leading Cause of Death in the U.S, Causing

More information

The aorta is an integral part of the cardiovascular system and should not be considered as just a conduit for blood supply from the heart to the

The aorta is an integral part of the cardiovascular system and should not be considered as just a conduit for blood supply from the heart to the The aorta is an integral part of the cardiovascular system and should not be considered as just a conduit for blood supply from the heart to the limbs and major organs. A range of important pathologies

More information

FFR and outcome: The mechanistic link

FFR and outcome: The mechanistic link FFR and outcome: The mechanistic link Bernard De Bruyne Cardiovascular Center Aalst Belgium Mechanisms of Plaque Destabilization Stenosis Hemodynamics Thrombotic Occlusion Blood/ Platelets Histopathology

More information

Ambiguity in Detection of Necrosis in IVUS Plaque Characterization Algorithms and SDH as Alternative Solution

Ambiguity in Detection of Necrosis in IVUS Plaque Characterization Algorithms and SDH as Alternative Solution Ambiguity in Detection of Necrosis in IVUS Plaque Characterization Algorithms and SDH as Alternative Solution Amin Katouzian, Ph.D., Debdoot Sheet, M.S., Abouzar Eslami, Ph.D., Athanasios Karamalis, M.Sc.,

More information

DECLARATION OF CONFLICT OF INTEREST. No disclosures

DECLARATION OF CONFLICT OF INTEREST. No disclosures DECLARATION OF CONFLICT OF INTEREST No disclosures micrornas: Role in progression of atherosclerosis Christian Weber Institute for Cardiovascular Prevention (IPEK) Ludwig-Maximilians-University Munich

More information

Spotty Calcification as a Marker of Accelerated Progression of Coronary Atherosclerosis : Insights from Serial Intravascular Ultrasound

Spotty Calcification as a Marker of Accelerated Progression of Coronary Atherosclerosis : Insights from Serial Intravascular Ultrasound Spotty Calcification as a Marker of Accelerated Progression of Coronary Atherosclerosis : Insights from Serial Intravascular Ultrasound Department of Cardiovascular Medicine Heart and Vascular Institute

More information

Hematocrit Level on Blood flow through a Stenosed Artery with Permeable Wall: A Theoretical Study

Hematocrit Level on Blood flow through a Stenosed Artery with Permeable Wall: A Theoretical Study Available at http://pvamu.edu/aam Appl. Appl. Math. ISSN: 1932-9466 Vol. 12, Issue 1 (June 2017), pp. 291-304 Applications and Applied Mathematics: An International Journal (AAM) Hematocrit Level on Blood

More information

actually rupture! Challenges to the vulnerable plaque concept

actually rupture! Challenges to the vulnerable plaque concept An Update on the Pathogenesis of the Acute Coronary Syndromes Peter Libby Brigham & Women s Hospital Harvard Medical School ADVANCES IN HEART DISEASE University of California San Francisco December 20,

More information

The Study of Endothelial Function in CKD and ESRD

The Study of Endothelial Function in CKD and ESRD The Study of Endothelial Function in CKD and ESRD Endothelial Diversity in the Human Body Aird WC. Circ Res 2007 Endothelial Diversity in the Human Body The endothelium should be viewed for what it is:

More information

Novel Reduction of PCSK9 Expression: Mechanistic Insights into the Anti-Atherosclerotic & Hypolipidemic Effects of Heat Shock Protein 27

Novel Reduction of PCSK9 Expression: Mechanistic Insights into the Anti-Atherosclerotic & Hypolipidemic Effects of Heat Shock Protein 27 Novel Reduction of PCSK9 Expression: Mechanistic Insights into the Anti-Atherosclerotic & Hypolipidemic Effects of Heat Shock Protein 27 Ed O Brien, Jean-Claude Bakala-N Goma, Chunhua Shi Cumming School

More information

Cho et al., 2009 Journal of Cardiology (2009), 54:

Cho et al., 2009 Journal of Cardiology (2009), 54: Endothelial Dysfunction, Increased Carotid Artery Intima-media Thickness and Pulse Wave Velocity, and Increased Level of Inflammatory Markers are Associated with Variant Angina Cho et al., 2009 Journal

More information

Novel function of NADPH oxidase in atherosclerosis. Yun Soo Bae Department of Life Science Ewha Womans University

Novel function of NADPH oxidase in atherosclerosis. Yun Soo Bae Department of Life Science Ewha Womans University Novel function of NADPH oxidase in atherosclerosis Yun Soo Bae Department of Life Science Ewha Womans University Recent understanding of ROS: act as second messengers e e Catalase/peroxidase O 2 H 2 O

More information

Cardiovascular Research Foundation and Columbia University Medical Center, New York.

Cardiovascular Research Foundation and Columbia University Medical Center, New York. Virtual Histology Intravascular Ultrasound Analysis of Non-culprit Attenuated Plaques Detected by Grayscale Intravascular Ultrasound in Patients with Acute Coronary Syndromes Xiaofan Wu, Akiko Maehara,

More information

IVUS Analysis. Myeong-Ki. Hong, MD, PhD. Cardiac Center, Asan Medical Center University of Ulsan College of Medicine, Seoul, Korea

IVUS Analysis. Myeong-Ki. Hong, MD, PhD. Cardiac Center, Asan Medical Center University of Ulsan College of Medicine, Seoul, Korea IVUS Analysis Myeong-Ki Hong, MD, PhD Cardiac Center, Asan Medical Center University of Ulsan College of Medicine, Seoul, Korea Intimal disease (plaque) is dense and will appear white Media is made of

More information

Lipoprotein Particle Profile

Lipoprotein Particle Profile Lipoprotein Particle Profile 50% of people at risk for HEART DISEASE are not identified by routine testing. Why is LPP Testing The Most Comprehensive Risk Assessment? u Provides much more accurate cardiovascular

More information

Effects of the angiotensin II type-1 receptor antagonist telmisartan on endothelial activation induced by advanced glycation endproducts

Effects of the angiotensin II type-1 receptor antagonist telmisartan on endothelial activation induced by advanced glycation endproducts Effects of the angiotensin II type-1 receptor antagonist telmisartan on endothelial activation induced by advanced glycation endproducts Serena Del Turco, Teresa Navarra, Giuseppina Basta, Raffaele De

More information

MinimallyModifiedLDLInducesActinPolymerization Macrophages viacd14signalingpathway.

MinimallyModifiedLDLInducesActinPolymerization Macrophages viacd14signalingpathway. MinimallyModifiedLDLInducesActinPolymerization Macrophages viacd14signalingpathway. *Randon T. Hall I, Joseph L. Witztum2, Yury I. Miller2 From the IMSTP-SURF Program and 2Division of Endocrinology and

More information

Potential mechanisms for the resolution of atherosclerosis by conjugated linoleic acid (CLA)

Potential mechanisms for the resolution of atherosclerosis by conjugated linoleic acid (CLA) HRB IMDA Oct HRB 2010 IMDA Seminar 28 th Oct 2010 Potential mechanisms for the resolution of atherosclerosis by conjugated linoleic acid (CLA) Dr. Orina Belton, School of Biomolecular and Biomedical Science,

More information

Multicenter Clinical Trial on the Impact of Biomechanical Factors on Bifurcation Stent Restenosis and Thrombosis

Multicenter Clinical Trial on the Impact of Biomechanical Factors on Bifurcation Stent Restenosis and Thrombosis 11th EBC, Athens, Greece September 25 & 26, 2015 Multicenter Clinical Trial on the Impact of Biomechanical Factors on Bifurcation Stent Restenosis and Thrombosis Yiannis S. Chatzizisis, MD, PhD Associate

More information

Statin Use and Cardiovascular Disease in HIV

Statin Use and Cardiovascular Disease in HIV Statin Use and Cardiovascular Disease in HIV Steven K. Grinspoon, MD Professor of Medicine Harvard Medical School Boston, Massachusetts FLOWED: 04/18/16 Los Angeles, California: April 25, 2016 Statin Use

More information

Fasting or non fasting?

Fasting or non fasting? Vascular harmony Robert Chilton Professor of Medicine University of Texas Health Science Center Director of Cardiac Catheterization labs Director of clinical proteomics Which is best to measure Lower continues

More information

Berries and Cardiovascular Health

Berries and Cardiovascular Health Berries and Cardiovascular Health Britt Burton-Freeman, PhD Institute for Food Safety and Health Illinois Institute of Technology bburton@iit.edu Berry Health Benefits Symposium Westlake Village CA, 2011

More information

1Why lipids cannot be transported in blood alone? 2How we transport Fatty acids and steroid hormones?

1Why lipids cannot be transported in blood alone? 2How we transport Fatty acids and steroid hormones? 1Why lipids cannot be transported in blood alone? 2How we transport Fatty acids and steroid hormones? 3How are dietary lipids transported? 4How lipids synthesized in the liver are transported? 5 Lipoprotien

More information

HEMODYNAMIC REGULATION OF ENDOTHELIAL CELL GENE. EXPRESSION: EFFECTS OF p65 EXPRESSION LEVEL ON. CONSTITUTIVE AND TNFα INDUCED NF-κB SIGNALLING

HEMODYNAMIC REGULATION OF ENDOTHELIAL CELL GENE. EXPRESSION: EFFECTS OF p65 EXPRESSION LEVEL ON. CONSTITUTIVE AND TNFα INDUCED NF-κB SIGNALLING HEMODYNAMIC REGULATION OF ENDOTHELIAL CELL GENE EXPRESSION: EFFECTS OF p65 EXPRESSION LEVEL ON CONSTITUTIVE AND TNFα INDUCED NF-κB SIGNALLING By Doyon Won A thesis submitted in conformity with the requirements

More information

Role of imaging in risk assessment models: the example of CIMT

Role of imaging in risk assessment models: the example of CIMT Role of imaging in risk assessment models: the example of CIMT Diederick E. Grobbee, MD, PhD, FESC Professor of Clinical Epidemiology Julius Center for Health Sciences and Primary Care, University Medical

More information

Supplementary figure 2. VCAM1 protein expression in static HCAECs exposed to CSE over 72 hours, with TNFα or TNFα + CSE positive controls.

Supplementary figure 2. VCAM1 protein expression in static HCAECs exposed to CSE over 72 hours, with TNFα or TNFα + CSE positive controls. Supplementary data Cigarette smoke extract profoundly suppresses TNFα-mediated proinflammatory gene expression through upregulation of ATF3 in human coronary artery endothelial cells Jack E. Teasdale 1,

More information

For unclear reasons, only about 40% of patients with calcific aortic stenosis also have coronary

For unclear reasons, only about 40% of patients with calcific aortic stenosis also have coronary Αθηροσκλήρωση και ασβεστοποιός στένωση της αορτικής βαλβίδας. Οµοιότητες και διαφορές Ν. Μεζίλης Κλινική «Άγιος Λουκάς» Ασβεστοποιός στένωση της αορτικής βαλβίδας: Μία ακόµα µορφή αθηρωµάτωσης; Some observations

More information

Microvascular Disease: How to Diagnose and What s its Treatment

Microvascular Disease: How to Diagnose and What s its Treatment Microvascular Disease: How to Diagnose and What s its Treatment Laxmi S. Mehta, MD, FACC The Ohio State University Medical Center Assistant Professor of Clinical Internal Medicine Clinical Director of

More information

Athérosclérose - Plaque Physiopathologie, Evaluation

Athérosclérose - Plaque Physiopathologie, Evaluation Athérosclérose - Plaque Physiopathologie, Evaluation Dr Philippe GAROT Institut Cardiovasculaire Paris Sud MASSY-QUINCY www.rcf-icps.com Mécanisme cellulaire Constitution de la plaque d athérome Monocytes

More information

Basic Mechanisms of Atherosclerosis and Plaque Rupture: Clinical Implications

Basic Mechanisms of Atherosclerosis and Plaque Rupture: Clinical Implications 12 th Annual Cardiovascular Disease Prevention Symposium February 8, 2013 KEYNOTE ADDRESS Basic Mechanisms of Atherosclerosis and Plaque Rupture: Clinical Implications Ira Tabas, M.D., Ph.D. Richard J.

More information

Prof. Peskin's DPA Scan & Advanced Lipid Analysis

Prof. Peskin's DPA Scan & Advanced Lipid Analysis Prof. Peskin's DPA Scan & Advanced Lipid Analysis Blood Chemistry: What s Important to me? Note: Enclosed are my results along with my personal opinions of these specific results. Again, they are my opinions

More information

Quantitative Real-Time PCR was performed as same as Materials and Methods.

Quantitative Real-Time PCR was performed as same as Materials and Methods. Supplemental Material Quantitative Real-Time PCR Quantitative Real-Time PCR was performed as same as Materials and Methods. Expression levels in the aorta were normalized to peptidylprolyl isomerase B

More information

The Site of Plaque Rupture in Native Coronary Arteries

The Site of Plaque Rupture in Native Coronary Arteries Journal of the American College of Cardiology Vol. 46, No. 2, 2005 2005 by the American College of Cardiology Foundation ISSN 0735-1097/05/$30.00 Published by Elsevier Inc. doi:10.1016/j.jacc.2005.03.067

More information

REAGENTS. RANDOX sdldl CHOLESTEROL (sdldl-c) SIZE MATTERS: THE TRUE WEIGHT OF RISK IN LIPID PROFILING

REAGENTS. RANDOX sdldl CHOLESTEROL (sdldl-c) SIZE MATTERS: THE TRUE WEIGHT OF RISK IN LIPID PROFILING REAGENTS RANDOX sdldl CHOLESTEROL (sdldl-c) SIZE MATTERS: THE TRUE WEIGHT OF RISK IN LIPID PROFILING Randox sdldl Cholesterol (sdldl-c) Size Matters: The True Wight of Risk in Lipid Profiling 1. BACKGROUND

More information

Depression and Subclinical Vascular Diseases in Psoriasis

Depression and Subclinical Vascular Diseases in Psoriasis Depression and Subclinical Vascular Diseases in Psoriasis Nehal N. Mehta, MD MSCE FAHA Section Chief, Inflammation and Cardiometabolic Diseases National Heart, Lung, and Blood Institute, USA Lasker Clinical

More information

Vascular Biology Anatomy and Function of Blood Vessels in Health Fig. 1.1 Endothelial Function Three Layers of Arteries

Vascular Biology Anatomy and Function of Blood Vessels in Health Fig. 1.1 Endothelial Function Three Layers of Arteries 1 Vascular Biology Scott Kinlay, MBBS, PhD, FACC, FRACP Vascular Biology applies to processes affecting arteries, veins, and other blood vessels. This chapter will focus on the physiology and pathophysiology

More information

Calcium Removal and Plaque Modification in the Era of DEB and Contemporary Stenting for Femoro- Popliteal Disease

Calcium Removal and Plaque Modification in the Era of DEB and Contemporary Stenting for Femoro- Popliteal Disease Calcium Removal and Plaque Modification in the Era of DEB and Contemporary Stenting for Femoro- Popliteal Disease Thomas M. Shimshak, MD Heart and Vascular Center Florida Hospital Heartland Medical Center

More information

Evaluation of Intermediate Coronary lesions: Can You Handle the Pressure? Jeffrey A Southard, MD May 4, 2013

Evaluation of Intermediate Coronary lesions: Can You Handle the Pressure? Jeffrey A Southard, MD May 4, 2013 Evaluation of Intermediate Coronary lesions: Can You Handle the Pressure? Jeffrey A Southard, MD May 4, 2013 Disclosures Consultant- St Jude Medical Boston Scientific Speaker- Volcano Corporation Heart

More information

Supplementary Information

Supplementary Information Nature Immunology doi:1.138/ni.2477 Supplementary Information Capillary and arteriolar pericytes attract innate leukocytes exiting through venules and instruct them with pattern recognition and motility

More information

University of Bristol - Explore Bristol Research

University of Bristol - Explore Bristol Research Teasdale, J. E., Hazell, G. G. J., Peachey, A. M. G., Sala-Newby, G. B., Hindmarch, C. C. T., McKay, T. R.,... White, S. J. (2017). Cigarette smoke extract profoundly suppresses TNF-mediated proinflammatory

More information

The PROSPECT Trial. A Natural History Study of Atherosclerosis Using Multimodality Intracoronary Imaging to Prospectively Identify Vulnerable Plaque

The PROSPECT Trial. A Natural History Study of Atherosclerosis Using Multimodality Intracoronary Imaging to Prospectively Identify Vulnerable Plaque The PROSPECT Trial Providing Regional Observations to Study Predictors of Events in the Coronary Tree A Natural History Study of Atherosclerosis Using Multimodality Intracoronary Imaging to Prospectively

More information

Coronary Heart Disease

Coronary Heart Disease Coronary Heart Disease Coronary Artery Wall Shear Stress Is Associated With Progression and Transformation of Atherosclerotic Plaque and Arterial Remodeling in Patients With Coronary Artery Disease Habib

More information

Glossary For TheFatNurse s For All Ages Series Apolipoprotein B (APOB or ApoB) are the primary apolipoproteins of chylomicrons and low-density lipoproteins (LDL - known commonly by the misnomer "bad cholesterol"

More information

Original Research Article

Original Research Article E-ISSN: 2378-654X Recent Advances in Biology and Medicine Original Research Article Intake of Moringa oleifera Leaf Extract Decreases IL-1 and TNF-α Levels in Dyslipidemic Wistar Rat Model HATASO, USA

More information

Simvastatin friend or foe in abdominal aortic aneurysm

Simvastatin friend or foe in abdominal aortic aneurysm Simvastatin friend or foe in abdominal aortic aneurysm A. Piechota-Polańczyk Department of Medical Biotechnology, Jagiellonian University, Krakow, Poland VISAR, Vienna, April 20-21, 2017 Statins in Abdominal

More information

Objectives. Acute Coronary Syndromes; The Nuts and Bolts. Overview. Quick quiz.. How dose the plaque start?

Objectives. 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 information

Dyslipidaemia. Is there any new information? Dr. A.R.M. Saifuddin Ekram

Dyslipidaemia. Is there any new information? Dr. A.R.M. Saifuddin Ekram Dyslipidaemia Is there any new information? Dr. A.R.M. Saifuddin Ekram PhD,FACP,FCPS(Medicine) Professor(c.c.) & Head Department of Medicine Rajshahi Medical College Rajshahi-6000 New features of ATP III

More information

La Trombosi Arteriosa

La Trombosi Arteriosa La Trombosi Arteriosa Prof. Giovanni Davì Medicina Interna Chieti Platelet activation and thrombosis Harrison 19 edizione Platelets are essential for primary hemostasis and repair of the endothelium They

More information

Targeting intracellular arginine / asymmetric dimethylarginine (ADMA).

Targeting intracellular arginine / asymmetric dimethylarginine (ADMA). Targeting intracellular arginine / asymmetric dimethylarginine (ADMA). From bench to practice: Novel anti-atherogenic strategies to improve endothelial function Rainer H. Böger, M.D. Institute of Clinical

More information

Curriculum Vitae. Research Officer in Baker IDI Heart & Diabetes Institute from Aug

Curriculum Vitae. Research Officer in Baker IDI Heart & Diabetes Institute from Aug Curriculum Vitae Yi Fu ( 付毅 ) (PhD, MBBS) Baker IDI Heart and Diabetes Institute 75 Commercial Road, Prahran, Melbourne, VIC 3004 Australia Phone: +61 3 8532 1288 Email: yi.fu@bakeridi.edu.au PROFILE Research

More information

Hypertriglyceridemia, Inflammation, & Pregnancy

Hypertriglyceridemia, Inflammation, & Pregnancy Hypertriglyceridemia, Inflammation, & Pregnancy Richard L. Nemiroff, MD, FACOG, NLA Professor, Clinical Gynecology Perelman School of Medicine University of Pennsylvania Philadelphia, PA Disclosure of

More information

Pathophysiology of Lipid Disorders

Pathophysiology of Lipid Disorders Pathophysiology of Lipid Disorders Henry Ginsberg, M.D. Division of Preventive Medicine and Nutrition CHD in the United States CHD is the single largest killer of men and women 12 million have history

More information

C-reactive protein. ; Friend or Foe? Ki Hoon Han MD PhD Asan Medical Center Seoul, Korea

C-reactive protein. ; Friend or Foe? Ki Hoon Han MD PhD Asan Medical Center Seoul, Korea C-reactive protein ; Friend or Foe? Ki Hoon Han MD PhD Asan Medical Center Seoul, Korea I. Inflammation and atherogenesis Atherosclerosis is an inflammatory disease Recruitment of Blood Monocytes by Endothelial

More information

Current Cholesterol Guidelines and Treatment of Residual Risk COPYRIGHT. J. Peter Oettgen, MD

Current Cholesterol Guidelines and Treatment of Residual Risk COPYRIGHT. J. Peter Oettgen, MD Current Cholesterol Guidelines and Treatment of Residual Risk J. Peter Oettgen, MD Associate Professor of Medicine Harvard Medical School Director, Preventive Cardiology Beth Israel Deaconess Medical Center

More information

Materials and Methods

Materials and Methods Short term hyperthermia prevents activation of proinflammatory genes in type B synoviocytes by blocking the activation of the transcription factor NF-κB Marica Markovic Institute of Medical Biochemistry,

More information

ACS pathophysiology: an Update חיים דננברג המרכז הרפואי הדסה ירושלים

ACS pathophysiology: an Update חיים דננברג המרכז הרפואי הדסה ירושלים ACS pathophysiology: an Update חיים דננברג המרכז הרפואי הדסה ירושלים Thrombus Formation and ACS Plaque Disruption/Fissure/Erosion Thrombus Formation Old Terminology: New Terminology: UA NQMI Non-ST-Segment

More information

Oral Disease as a Risk Factor for Acute Coronary Syndrome Single Center Experience

Oral Disease as a Risk Factor for Acute Coronary Syndrome Single Center Experience 1167 International Journal of Collaborative Research on Internal Medicine & Public Health Oral Disease as a Risk Factor for Acute Coronary Syndrome Single Center Experience Sachin Kumar Amruthlal Jain

More information