Talk:Cardiovascular System - Coronary Circulation Development

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Cite this page: Hill, M.A. (2020, October 30) Embryology Cardiovascular System - Coronary Circulation Development. Retrieved from


Coronary Artery Development: Progenitor Cells and Differentiation Pathways

Annu Rev Physiol. 2017 Feb 10;79:1-19. doi: 10.1146/annurev-physiol-022516-033953. Epub 2016 Dec 9.

Sharma B1, Chang A1,2, Red-Horse K1.


Coronary artery disease (CAD) is the number one cause of death worldwide and involves the accumulation of plaques within the artery wall that can occlude blood flow to the heart and cause myocardial infarction. The high mortality associated with CAD makes the development of medical interventions that repair and replace diseased arteries a high priority for the cardiovascular research community. Advancements in arterial regenerative medicine could benefit from a detailed understanding of coronary artery development during embryogenesis and of how these pathways might be reignited during disease. Recent research has advanced our knowledge on how the coronary vasculature is built and revealed unexpected features of progenitor cell deployment that may have implications for organogenesis in general. Here, we highlight these recent findings and discuss how they set the stage to interrogate developmental pathways during injury and disease. KEYWORDS: blood flow; coronary artery; endocardium; sinus venosus; vascular remodeling

PMID 27959616 DOI: 10.1146/annurev-physiol-022516-033953


The anatomy and development of normal and abnormal coronary arteries

Cardiol Young. 2015 Dec;25(8):1493-503. doi: 10.1017/S1047951115001390.

Spicer DE1, Henderson DJ2, Chaudhry B2, Mohun TJ3, Anderson RH2.


At present, there is significant interest in the morphology of the coronary arteries, not least due to the increasingly well-recognised association between anomalous origin of the arteries and sudden cardiac death. Much has also been learnt over the last decade regarding the embryology of the arteries. In this review, therefore, we provide a brief introduction into the recent findings regarding their development. In particular, we emphasise that new evidence, derived using the developing murine heart, points to the arterial stems growing out from the adjacent sinuses of the aortic root, rather than the arteries growing in, as is currently assumed. As we show, the concept of outgrowth provides an excellent explanation for several of the abnormal arrangements encountered in the clinical setting. Before summarising these abnormal features, we draw attention to the need to describe the heart in an attitudinally appropriate manner, following the basic rule of human anatomy, rather than describing the cardiac components with the heart in the "Valentine" orientation. We then show how the major abnormalities involving the coronary arteries in humans can be summarised in terms of abnormal origin from the pulmonary circulation, abnormal aortic origin, or fistulous communications between the coronary arteries and the cardiac cavities. In the case of abnormal aortic origin, we highlight those malformations known to be associated with sudden cardiac death. KEYWORDS: Abnormal aortic origin; abnormal pulmonary origin; circumflex artery; left coronary artery; right coronary artery

PMID 26675596


Coronary arteries form by developmental reprogramming of venous cells

Nature. 2010 Mar 25;464(7288):549-53.

Red-Horse K, Ueno H, Weissman IL, Krasnow MA.

Department of Biochemistry and Howard Hughes Medical Institute, Stanford, California 94305-5307, USA. Comment in:

Nat Rev Mol Cell Biol. 2010 May;11(5):312. Nature. 2010 Mar 25;464(7288):498-9. Abstract Coronary artery disease is the leading cause of death worldwide. Determining the coronary artery developmental program could aid understanding of the disease and lead to new treatments, but many aspects of the process, including their developmental origin, remain obscure. Here we show, using histological and clonal analysis in mice and cardiac organ culture, that coronary vessels arise from angiogenic sprouts of the sinus venosus-the vein that returns blood to the embryonic heart. Sprouting venous endothelial cells dedifferentiate as they migrate over and invade the myocardium. Invading cells differentiate into arteries and capillaries; cells on the surface redifferentiate into veins. These results show that some differentiated venous cells retain developmental plasticity, and indicate that position-specific cardiac signals trigger their dedifferentiation and conversion into coronary arteries, capillaries and veins. Understanding this new reprogramming process and identifying the endogenous signals should suggest more natural ways of engineering coronary bypass grafts and revascularizing the heart.

PMID: 20336138

Retinoic acid and VEGF delay smooth muscle relative to endothelial differentiation to coordinate inner and outer coronary vessel wall morphogenesis

Azambuja AP, Portillo-Sánchez V, Rodrigues MV, Omae SV, Schechtman D, Strauss BE, Costanzi-Strauss E, Krieger JE, Perez-Pomares JM, Xavier-Neto J. Circ Res. 2010 Jul 23;107(2):204-16. Epub 2010 Jun 3. PMID: 20522805

The sinus venosus progenitors separate and diversify from the first and second heart fields early in development

Mommersteeg MT, Domínguez JN, Wiese C, Norden J, de Gier-de Vries C, Burch JB, Kispert A, Brown NA, Moorman AF, Christoffels VM. Cardiovasc Res. 2010 Jul 1;87(1):92-101. Epub 2010 Jan 28. PMID: 20110338

Excellent functional result in children after correction of anomalous origin of left coronary artery from the pulmonary artery--a population-based complete follow-up study

Ojala T, Salminen J, Happonen JM, Pihkala J, Jokinen E, Sairanen H. Interact Cardiovasc Thorac Surg. 2010 Jan;10(1):70-5. Epub 2009 Oct 6.

Surgical strategy to construct a two-coronary system for a patient with anomalous origin of left coronary artery from pulmonary artery (ALCAPA) has evolved with time. Limited long-term follow-up data are available on these children. We report population-based follow-up in children operated on for ALCAPA. In total, 29 patients underwent aortic reimplantation of ALCAPA between 1979 and 2006. Twenty (69%) children were repaired with direct aortic implantation, five (17%) with a modified tubular extension technique, and four (14%) patients with an intrapulmonary baffling technique. Early postoperative mortality (<30 days) was 17%. No late mortality (>30 days) was detected. The median length of follow-up was 11 years (range 10 months-27 years). Global left ventricular function by echocardiography (M-mode) was within normal limits (>30%) in all patients one year after operation. Functionally, 80% of patients were classified in NYHA class I, 20% in NYHA II, and 0% in NYHA classes III/IV at the time of the last examination. Excellent results with good long-term outcome can be achieved in infants with ALCAPA using reimplantation techniques. Normalization of cardiac function is expected within the first year in all operative survivors with a patent coronary system.

PMID: 19808708


The venous drainage of the human myocardium

Adv Anat Embryol Cell Biol. 2003;168:I-VIII, 1-104. von Lüdinghausen M.

Institut für Anatomie und Zellbiologie, Universität Würzburg, Koellikerstr. 6, 97070 Würzburg, Germany. anat033@mail.uni-wuerzburg.deauthorinfo Abstract New cardiological techniques such as coronary sinus catheterization and selective catheterization of the cardiac veins permit the opening of new experimental and clinical fields, for instance in venous angiography and the reverse nourishment of myocardium which is endangered by ischemia,and also in the electrophysiological study of the components of the conduction system. New approaches in heart surgery, such as the removal of accessory pathways of the conduction system (as in WPW syndrome), necessitate the realization of the topographical relationships of the vessels in the various sections of the coronary sulci in a different way. The objective of this work is, therefore, to present comprehensive and almost new macro- and microanatomical data about the venous drainage of the myocardium via the coronary sinus and its related and unrelated (non-coronary) cardiac veins. Examination of meticulously dissected heart specimens (of individuals who had achieved old or extreme old age at the time of their death in Germany: n=250) as well as corrosion casts of adult cardiac vessels (of individuals of all ages, n=25) formed the basis for the exact description and documentation of the occurrence, frequency, origin, and courses of both the normal and anomalously developed human coronary sinus and cardiac veins. A wide range of morphological and experimental references was consulted in order to enable thorough discussion of the anatomical findings in the light of modern cardiological diagnostics and treatment. The anatomical and clinical nomenclature is presented and there is a brief comment on modern diagnostic techniques and their applications where the cardiac veins are concerned. The two principal and one compound cardiac venous system are defined and discussed with reference to the existence of both the normal and anomalous coronary sinus and cardiac vein. 1. The greater (major) cardiac venous system (2) The smaller (minor) cardiac venous system (3)The compound cardiac venous system. The microanatomy of the various proper cardiac veins is not very well explained and illustrated in old or new literature; therefore, special attention is paid in the present study to the detailed microanatomy of the cardiac venous drainage. This includes the topograpy and structural and surface anatomy of the coronary sinus (position, length and shape, diameters, area of cross-section, circumference and volume, curvature, elevation, ostial angle, enlargement, duplication, absence), and the exact enternal and internal morphological landmarks of the coronary sinus with reference to its myocardial cover, isolated myocardial belts, and "free" myocardial cords which connect the atrial and ventricular myocardium, and the atrial ostium of the coronary sinus. It is established that the frequency, distribution pattern, courses and mode of opening of the major ventricular and atrial cardiac veins and the occurrence, morphology, and efficiency of the ostial valves of the coronary sinus and its tributaries all influence the success of any selective catheter implantation and venous reperfusion technique to a great degree. There are many peculiarities of the cardiac veins which are worthy of consideration, for instance intramyocardial and aberrant courses of the anterior interventricular vein, the oblique vein of the left atrium, the posterior interventricular vein, the small cardiac vein, the posterior vein of the left ventricle, the left and right marginal veins, and the anterior cardiac veins. Various forms and courses of the intramural venous tunnel, sinus or channel of the right atrium were found and illustrated, and discussed in terms of developmental and comparative anatomy. This review incorporates a great variety of clinically significant, new morphological findings with regard to the coronary sinus and the cardiac venous system. The many anatomical peculiarities and hindrances to the catheterization of the coronary sinus and the reperfusion of (even selected) cardiac veins are documented and evaluated; the various problems which may arise in venous reperfusion due to the presence of anatomical anomalies of the coronary sinus, cardiac veins, and ostial valves (of greater or lesser efficiency) are addressed. The presentation narrows a gap in the rather incomplete knowledge of the venous drainage of the human myocardium.

PMID: 12645157


Development of the coronary arteries in the embryonic human heart

Hutchins GM, Kessler-Hanna A, Moore GW

Circulation 1988 Jun;77(6):1250-7

It is not known why the coronary arteries almost always originate only from the right and left aortic sinuses of Valsalva, since the structure and conditions appear to be the same for all six sinuses of the embryonic great arteries. We sought a possible mechanical explanation for the phenomenon by studying the development of the coronary vasculature in 351 staged, serially sectioned human embryos of Carnegie stages 9 through 23 from the Carnegie Embryological Collection. A plexus of blind epicardial capillaries appears on the heart in Carnegie stage 14 or 15 and acquires a coronary sinus connection in stage 15, 16, or 17. The connection of the proximal coronary arteries to the aorta does not appear until stage 18. We found no histologic features of the cardiac nerves or any other component of the tissues to account for the consistent origin of coronary arteries from the right and left aortic sinuses of Valsalva. However, serial section reconstructions showed that the two sinuses where coronary arteries develop acquire a positive transverse curvature and a negative longitudinal curvature, i.e., a catenoidal or saddle-shaped configuration, before the appearance of the coronary arteries. The four noncoronary sinuses also have a positive transverse curvature, but longitudinally, in contrast, they have a positive curvature or are straight. The results suggest that the coronary arteries originate from those sinuses of Valsalva where wall tension is increased by a catenoidal configuration.

PMID: 3286038, UI: 88223706