Role of growth factors in coronary morphogenesis.
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This communication briefly reviews the role of angiogenic growth factors in myocardial vessel formation during development. The earliest signs of vascularization are the migration and differentiation of angioblasts from the epicardium and subepicardium into the myocardium. A regulator of this process is vascular endothelial growth factor (VEGF), which is probably triggered by hypoxia. The subsequent formation of vascular tubes is regulated by multiple growth factors: VEGF family members, fibroblast growth factors (FGFs), and angiopoietins and their receptors. Our studies on explanted quail hearts reveal that these growth factors are interdependent. We also have shown that a harmonic interplay of growth factors characterizes early postnatal development in rats. Neutralizing antibodies to either basic FGF (bFGF) or VEGF inhibit capillary formation, whereas arteriolar growth is markedly inhibited by bFGF, but not VEGF, neutralizing antibodies. Arteriolar diameter is also increased when anti-bFGF and anti-VEGF are administered in combination. Thus, the hierarchical development of the arteriolar vasculature depends on both of these growth factors; however, the establishment of arterioles, as reflected by length density, is dependent on bFGF but not on VEG. Finally, stretch of cardiac myocytes and endothelial cells serves as a stimulus for increases in growth factor and receptor proteins. We have shown that cyclic stretch of either cell type increases VEGF, and that endothelial cells respond to stretch by up-regulation of VEGF receptor-2 (VEGFR-2), and Tie-2 receptor. These results indicate that both mechanical and metabolic factors are primary stimuli for coronary angiogenesis. (+info)
The role of the epicardium and neural crest as extracardiac contributors to coronary vascular development.
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At species-specific times in embryonic development, the pro-epicardial organ appears as an outcropping of the mesothelial body wall, near the sinus venosus-liver region. The pro-epicardial vesicles attach to the myocardium, flatten, and join to form the epicardium. The epicardium shows epithelial-mesenchymal transformation: cells detach from the epithelium, fill the subepicardial space, and invade the heart tube. Epicardium-derived cells migrate as far as the core of the endocardial cushions, which differentiate into the atrioventricular valve leaflets. In the cardiac wall, other epicardium-derived cells differentiate into interstitial fibroblasts and adventitial and smooth muscle cells of the coronary arteries. Using neural crest tracings in mouse embryos (Wnt1-Cre-lacZ), we studied the patterning of cardiac neural crest cells during development. Participation of neural crest cells in the formation of the vascular media could not be excluded, although epicardium-derived cells have hitherto been considered responsible for formation of the coronary arterial smooth muscle cells. The endothelial cells of the coronary network derive mostly from the endothelium of the sinus venosus-liver region by vasculogenesis and angiogenesis. However, an epicardium-derived cell origin of some endothelial cells cannot be ruled out. The coronary vasculature is closely related to the differentiating Purkinje network, but isolated epicardium-derived cells are also associated with Purkinje cells. After ablating the pro-epicardial organ in quail embryos, we found severe malformations in the myocardial architecture, leading to the hypothesis that epicardium-derived cells give instructive signals to the myocardium for proper differentiation of the compact and the trabeculated compartments. (+info)
Coronary arteriogenesis and differentiation of periarterial Purkinje fibers in the chick heart: is there a link?
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In the following review, we outline the cellular ontogeny and time course of coronary artery development within the vertebrate heart. Our eventual focus will be the potential role of arteriogenesis in the differentiation of a subset of specialized conduction cells in the chick heart. We begin by briefly outlining early heart formation, showing how the outermost layer of the looped, tube heart--the epicardium--is of extracardiac origin and provides the progenitor cells to the entire vascular bed. Subsequently, we summarize the events of coronary arterial development that follow epicardialization. Finally, we discuss work in the chick that indicates how arteries form pioneering, directional conduits through ventricular tissue, adjacent to which myocardial cells differentiate to form the most peripheral component of the avian conduction system--a network of periarterial Purkinje fibers. (+info)
The study of coronary artery anomalies would benefit from the clarification of various fundamental issues, including the definitions, classification, incidence, pathophysiologic mechanisms, and clinical relevance of each anomaly. The greatest challenge is to identify the abnormality and determine its clinical relevance so that appropriate treatment can be instituted. Currently, the coronary anatomy is essentially defined by the features of the (conductive) epicardial coronary tree and its dependent territory. Therefore, one must consider all the possible and observed variations in anatomic features that are used to describe the coronary arteries. We propose that the left anterior descending, circumflex, and right coronary arteries be considered the essential elementary units of coronary anatomy. We also suggest that the coronary arteries be defined not by their origin or proximal course, but by their intermediate and distal segments or dependent microvascular bed. A strict classification system is necessary before meaningful data can be gathered about the incidence of coronary anomalies. With respect to clinical relevance, the greatest challenge is presented by anomalies that only occasionally cause critically severe clinical events and are otherwise compatible with a normal life. In such cases, it is not known whether the specific features of a given anomaly cause adverse clinical consequences, or whether additional episodic factors are required. To correlate subclassifiable anatomic and functional features with clinical events and prognoses, a large, multicenter database, relying on prospective, coordinated protocols, is urgently needed. In the absence of established official guidelines, we present practical protocols for diagnosing and treating coronary anomalies. (+info)
Congenital heart defects and coronary anatomy.
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Coronary artery anomalies are a well recognized feature of many cardiac malformations and have been catalogued in a number of reviews. This overview concentrates on 1) the interplay between congenital heart defects and coronary morphogenesis, examining how some of the embryology fits with the experiments of nature encountered in clinical practice; and 2) the influence of coronary anatomy on patient management. This overview uses, as examples, pulmonary atresia with intact ventricular septum, complete and congenitally corrected transpositions of the great arteries, and tetralogy of Fallot. (+info)
Surgical treatment of coronary artery anomalies: report of a 37 1/2-year experience at the Texas Heart Institute.
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The surgical treatment of coronary artery anomalies continues to evolve. The most common coronary artery anomalies requiring surgical intervention include coronary artery fistulae, anomalous pulmonary origins of the coronary arteries, and anomalous aortic origins of the coronary arteries. The choice of surgical intervention for each type of coronary anomaly depends on several anatomic, physiologic, and patient-dependent variables. As surgical techniques have progressed, outcomes have continued to improve, however, controversy still exists about many aspects of the proper management of patients who have these coronary artery anomalies. We reviewed the surgical treatment of 178 patients who underwent surgery for the above-mentioned types of coronary artery anomalies at the Texas Heart Institute from December 1963 through June 2001. On the basis of this experience, we discuss historical aspects of the early treatment of these anomalies and describe their present-day management. (+info)
Can stent-angioplasty be a valid alternative to surgery when revascularization is indicated for anomalous origination of a coronary artery from the opposite sinus?
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When intervention is indicated for anomalous origination of a coronary artery from the opposite sinus, stent-angioplasty may seem more attractive than coronary artery bypass grafting. However, in the case of anomalous origination of a coronary artery from the opposite sinus, the anatomy is quite different from that encountered in atherosclerotic disease, and stent-angioplasty would involve unusual challenges, both in technique and prognostic outcomes. We illustrate these points by presenting the 2 first cases in which intervention was indicated because of severe symptoms. We conclude from this preliminary study that coronary artery bypass grafting should still be considered the preferred (although unproven) method of revascularization in patients who have symptomatic anomalous origination of a coronary artery from the opposite sinus. Until adequate data have been gathered to evaluate the late results of stent-angioplasty in these patients (in comparison with the results of surgical and medical treatment), the procedure should be performed only in selected patients, enrolled in prospective, controlled studies. (+info)
Meandering right pulmonary vein to the left atrium and inferior vena cava: the first case with associated anomalies.
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We report a case of a healthy, asymptomatic 6-year-old boy in whom an anomalous right pulmonary vein was noted to drain into both the inferior vena cava and left atrium in association with findings consistent with scimitar syndrome. The anomalous pulmonary vein took a very circuitous route through the lungs before draining into the left atrium, a condition previously termed "meandering pulmonary vein." To aid in the diagnosis, cardiovascular magnetic resonance imaging and magnetic resonance angiography were used to delineate this complex course and the connection of the anomalous pulmonary vein. To our knowledge, this is the 1st reported case of a meandering pulmonary vein with dual drainage to the inferior vena cava and left atrium in association with other anomalies. (+info)