Heart 3: Organogenesis, CHD, prenatal circulation
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1 Heart 3: Organogenesis, CHD, prenatal circulation Heart development Development of vasculature Pathogenesis of CHD Prenatal circulation and its remodeling after birth David Sedmera Charles University First Faculty of Medicine Institute of Anatomy
2 Molecular control of cardiogenesis
3 Formation of the heart tube
4 Morphogenesis of the heart
5 Cardiac tube & its looping
6 Septation of atria and ventricles
7 Morfogenetic mechanisms Proliferation Migration Diferentiation Cell death (programmed)
8 Outflow tract septation
9 Role of neural crest in outflow tract septation NB coronary vessels also have extracardiac origin
10 Analysis of neural crest cell migration using chick - quail chimera aortico-pulmonary septum!
11 Electrocardiogram (ECG)
12 Embryonic conduction system RA LA RV LV
13 Visualization of embryonic CCS Isochronal activation maps Conserved among species (homeioterms)
14 Development of coronary vessels
15 EPDCs
16 Congenital heart disease Cardiac tube - cardia bifida (lethal) Impaired looping - dextrocardia Deficient septation - ASD, VSD Outflow tract defects - PTA, DORV, TGA TOF (cyanotic, common, complex) PDA (relatively common, extracardiac) Causes: genetics (Down s, Nkx2.5 mutations), environment / drugs (ethanol, Etretinate, )
17 Factors influencing development Genetic (dominant and recessive alleles, interactions, variants ) Physical (mechanical, ionizing radiation, temperature, hypoxia) Chemical (teratogens, ionic disequilibrium, vitamins, hormonal dysbalance, hyperglycemia ) Biological (bacteria, viruses, parasites)
18 Chick embryonic model
19 Hypoplastic left heart syndrome (HLHS)
20 Vasculogenesis vs. Angiogenesis
21 Origin of endothelial cells 1. Mesenchyme precursor cell (hemangioblast, prumary angioblast, determined by FGF) Lokalization: Extraembryonic yolk sac intraembryonic mesoderm - somites, splanchnopleura alantois?
22 Blood islands Vessels de novo vaskulogenesis C-myb
23
24 Vasculogenesis
25 Aortico-gonadal region Formation of blood and endothelial cells in ventral aortic wall HC - CD 45 + EC - VEGFR2+
26 Hematopoiesis during prenatal development
27 Angiogenesis Sprouting Tip formation Migration Lumen formation Connection Establishment of flow Pericytes Vessel maturation
28 Mechanisms of angiogenesis 1) intususception growth 2) intercalar growth 3) fusion 5) remodling 6) pruning
29 Organotypic endotelial diferentiation interaction with parenchymal cells Pores and fenestrations Specific receptors and enzymes
30 Pro-Angiogenic growth factors VEGF (vascular endothelial gowth factor) A, - B, - C, - D, - E PlGF (placental growth f.), PDGF (platelet derived growth f.) GF receptors: (RTK activity) VEGFR-1 (Flt1) VEGFR-2 (Flk1, KDR, Quek1) VEGFR-3 (Flt-4, Quek2)
31
32 VEGF A - VEGFR 2 different isoforms of VEGF A (alternative splicing) increases permeability expression stimulated by hypoxia
33 VEGF B - VEGFR 1 heart and skeletal muscle not dependent on tissue hypoxia VEGF C - VEGFR 3 proliferation of lymphatic endothelium
34 More angiogenic growth factors: Angiopoetin -1, -2 / receptor Tie 1, Tie 2 structural vessel integrity Remodling, cell adhesion Ang 1 emrbyonic Ang 2 adulthood in areas of active remodeling
35 Defect of Tie2 receptor
36 Determination of arterio-venous identity: Ephrin B2 / receptor EphB4
37 Vessels and nerves growth together (same signaling molecules)
38 Lymfangiogenesis GF and receptor: VEGF-C VEGFR-3 Transcription factor Prox1 Syk / SLP 76??
39 Aortic arch derivatives I II III a. maxillaris a. hyoidea, a. stapedia a. carotis communis, první úsek a. carotis interna IV Aortic arch from a. carotis communis to a. subclavia sin. VI a. subclavia dx.(proximal segment) a. pulmonalis sin., ductus arteriosus a. pulmonalis dx.
40
41 Right-sided aortich arch (!standard in birds)
42 Coarctation of the aorta (pre and post ductal type, collateral circulation
43 Anomalous origin retreoesophageal right subclavian artery (a. lusoria)
44 Double aortic arch can cause breathing or swallowing difficulties
45 in utero Fetal and postnatal circulation
46 Fetal and postnatal circulation Remodeling after birth post partum
47 References Milan Klima (heart picture) Sadler: Human Embryology Ondrej Nanka (angiogenesis) Original research papers Venous system development:
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