Cardiovascular System - Coronary Circulation Development

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Human embryo coronary sinus (stage 22)
Adult heart coronary arteries

The coronary circulation provides the blood supply to the heart required for the normal muscular function. From recent mouse studies, the origin of this specialised vasculature is from the sinus venosus.

Development of the heart and vascular system begins very early in mesoderm both within (embryonic) and outside (extra embryonic) the embryo. Vascular development therefore occurs in many places, the most obvious though is the inflow and outflow in the forming heart, which grows rapidly creating an externally obvious cardiac "bulge" on the early embryo.

The coronary circulation an important medical topic postnatally. Blockage and failure of this system leads initially to angina, continued ischemia leads to hypoxic death of cardiac muscle and myocardial infarction, a heart attack.

For general information about blood vessel development, see Blood Vessel Development and note that blood vessels also occurs outside the embryo in the extra-embryonic mesoderm of the yolk sac (vitelline) and in the villi of the placenta.

Cardiovascular Links: cardiovascular | Heart Tutorial | Lecture - Early Vascular | Lecture - Heart | Movies | 2016 Cardiac Review | heart | coronary circulation | heart valve | heart rate | Circulation | blood | blood vessel | blood vessel histology | heart histology | Lymphatic | ductus venosus | spleen | Stage 22 | cardiovascular abnormalities | OMIM | 2012 ECHO Meeting | Category:Cardiovascular
Historic Embryology - Cardiovascular 
1902 Vena cava inferior | 1905 Brain Blood Vessels | 1909 Cervical Veins | 1909 Dorsal aorta and umbilical veins | 1912 Heart | 1912 Human Heart | 1914 Earliest Blood-Vessels | 1915 Congenital Cardiac Disease | 1915 Dura Venous Sinuses | 1916 Blood cell origin | 1916 Pars Membranacea Septi | 1919 Lower Limb Arteries | 1921 Human Brain Vascular | 1921 Spleen | 1922 Aortic-Arch System | 1922 Pig Forelimb Arteries | 1922 Chicken Pulmonary | 1923 Head Subcutaneous Plexus | 1923 Ductus Venosus | 1925 Venous Development | 1927 Stage 11 Heart | 1928 Heart Blood Flow | 1935 Aorta | 1935 Venous valves | 1938 Pars Membranacea Septi | 1938 Foramen Ovale | 1939 Atrio-Ventricular Valves | 1940 Vena cava inferior | 1940 Early Hematopoiesis | 1941 Blood Formation | 1942 Truncus and Conus Partitioning | Ziegler Heart Models | 1951 Heart Movie | 1954 Week 9 Heart | 1957 Cranial venous system | 1959 Brain Arterial Anastomoses | Historic Embryology Papers | 2012 ECHO Meeting | 2016 Cardiac Review | Historic Disclaimer

Some Recent Findings

  • Review - Coronary Artery Development[1] "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."
  • Review - anatomy and development of normal and abnormal coronary arteries[2] "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."
  • Coronary arteries form by developmental reprogramming of venous cells [3] "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."
  • Developmental coronary maturation is disturbed by aberrant cardiac vascular endothelial growth factor expression and Notch signalling[4] "In vitro, human arterial coronary endothelial cells were treated with VEGF121 or VEGF165 upon which RT-qPCR was performed. In vivo, mutant coronary arterial endothelium showed a decrease in protein expression of arterial markers such as cleaved Notch1, Delta-like4, and ephrinB2 concomitant with an increase of venous markers such as chicken ovalbumin upstream promoter transcription factor II. The venous endothelium showed the opposite effect, which was confirmed on the mRNA level."
More recent papers  
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Search term: Coronary Circulation Embryology

Fabio Da Silva, Filippo Massa, Fariba Jian Motamedi, Valerie Vidal, Ana Sofia Rocha, Elodie P Gregoire, Chen-Leng Cai, Kay Dietrich Wagner, Andreas Schedl Myocardial-specific R-spondin3 drives proliferation of the coronary stems primarily through the Leucine Rich Repeat G Protein coupled receptor LGR4. Dev. Biol.: 2018; PubMed 29859889

Alexandros P Patrianakos, Adam Hatzidakis, Maria Marketou, Fragiskos I Parthenakis Adult-type ALCAPA syndrome: A rare coronary artery anomaly. Echocardiography: 2018, 35(7);1056-1059 PubMed 29749648

Parag Bhalgat, Abhijeet Naik, Prasanna Salvi, Nilesh Bhadane, Kshiti Shah, Bhawan Paunipagar, Suresh Joshi Cardiac magnetic resonance imaging, myocardial scar and coronary flow pattern in anomalous origin of left coronary artery from the pulmonary artery. Indian Heart J: 2016, 70(2);303-307 PubMed 29716711

Kahraman Yakut, Kürşad Tokel, Birgül Varan, İlkay Erdoğan, Murat Özkan [Case report and the surgical treatment of two cases with pulmonary atresia in which pulmonary arteries is circulated by coronary arteries]. [Pulmoner arter kanlanması koroner arterler yoluyla olan pulmoner atrezili iki olgu sunumu ve cerrahi tedavisi.] Turk Kardiyol Dern Ars: 2018, 46(3);216-220 PubMed 29664428

Ch Bharat Siddharth, Mayank Yadav, Amol Bhoje, Milind P Hote Dual drainage total anomalous pulmonary venous connection: a rare mixed variant. Asian Cardiovasc Thorac Ann: 2018, 26(4);305-307 PubMed 29649881

Coronary Vessel Anatomy

Coronary Arteries

Three aortic sinuses, or sinuses of Valsalva, are the left, right and posterior that give rise to the two coronary arteries, the posterior aortic sinus is the non-coronary sinus.
  • Right coronary artery (RCA) from the right aortic sinus
  • Left coronary artery (LCA) from the left aortic sinus
Coronary Arteries Aortic Arch

Coronary Veins

  • Great Cardiac Vein (left coronary vein) - empty directly into the coronary sinus
  • Coronary sinus - empty directly into the right atrium.
  • Anterior cardiac veins - empty directly into the right atrium.
Coronary Veins

Human Coronary Vessel Development

An early research paper identified development of the coronary arteries in the embryonic human heart using embryos from the Carnegie Collection.[5]

  • six sinuses of the embryonic great arteries
  • Carnegie Embryological Collection coronary vasculature in 351 staged, serially sectioned human embryos (Carnegie stages 9 to 23).

stage 14 or 15 - A plexus of blind epicardial capillaries appears on the heart in Carnegie

stage 15, 16, or 17 - acquires a coronary sinus connection

stage 18 - connection of the proximal coronary arteries to the aorta.

Mouse Coronary Vessel Development

Mouse-coronary vessel formation.jpg

Image showing changes in venous (blue) and arterial (red) marker expression during coronary development; black indicates dedifferentiated venous cells.[3]


There are several abnormalities associated with the anatomical variation in vascular pattern of vessels including abnormal origins and absence.


The image shows a human coronary sinus defect as viewed from the left atrial aspect.

There is a persistent left superior caval vein (SCV) opening to the leftward and cranial margin of the left atrium. The caval vein would normally have been incorporated into the left atrioventricular groove, but the walls which would normally extend to its opening to the right atrium (black dotted lines) have disappeared. Note the integrity of the oval fossa.

Anomalous Left Coronary Artery from the Pulmonary Artery

Anomalous origin of left coronary artery from pulmonary artery (ALCAPA) is a rare malformation (incidence of 0.25–0.50% )in children with abnormal cardiac development leading to a mortality rate of 90% in unoperated infants.[6] There are a variety of surgical repair techniques including: direct aortic implantation, a modified tubular extension technique, and an intrapulmonary baffling technique.[7]

Anomalous Right Coronary Artery from the Left Sinus

Anomalous Single Coronary Artery from the left sinus of Valsalva

This abnormality has been reported as occurring with an absence of the right coronary artery. [8]

Ectopic Origin of the Right Coronary Artery

The right coronary artery arises outside the borders of the right coronary sinus, the most common locations are the left sinus (either the anterior, superior portion) or directly from the left main coronary artery. Anterior displacement is the most prevalent anatomical variant.[9] Also very rarely arising from other anatomical locations including; the non-coronary (posterior) sinus, left anterior descending coronary artery, left circumflex coronary artery, pulmonic artery, and the descending aorta. Clinically seen as cardiac ischemia and arrhythmia.

Anomalous Sinus Node Artery

The sinus node artery normally originates from the proximal segment of the right coronary artery, left circumflex artery, or from both. With anomalous sinus node artery this vessel can originate from the left anterior descending artery.

Congenital Sinus of Valsalva Aneurysm

This aneurysm, a blood-filled dilatation, arises due to a localized weakness of the wall of the sinus bulging that may rupture into an adjacent cardiac chamber, forming an aortocardiac fistula.


  1. Bikram Sharma, Andrew Chang, Kristy Red-Horse Coronary Artery Development: Progenitor Cells and Differentiation Pathways. Annu. Rev. Physiol.: 2017, 79;1-19 PubMed 27959616
  2. Diane E Spicer, Deborah J Henderson, Bill Chaudhry, Timothy J Mohun, Robert H Anderson The anatomy and development of normal and abnormal coronary arteries. Cardiol Young: 2015, 25(8);1493-1503 PubMed 26675596
  3. 3.0 3.1 Kristy Red-Horse, Hiroo Ueno, Irving L Weissman, Mark A Krasnow Coronary arteries form by developmental reprogramming of venous cells. Nature: 2010, 464(7288);549-53 PubMed 20336138
  4. Nynke M S van den Akker, Vincenza Caolo, Lambertus J Wisse, Patricia P W M Peters, Robert E Poelmann, Peter Carmeliet, Daniël G M Molin, Adriana C Gittenberger-de Groot Developmental coronary maturation is disturbed by aberrant cardiac vascular endothelial growth factor expression and Notch signalling. Cardiovasc. Res.: 2008, 78(2);366-75 PubMed 18093989
  5. G M Hutchins, A Kessler-Hanna, G W Moore Development of the coronary arteries in the embryonic human heart. Circulation: 1988, 77(6);1250-7 PubMed 3286038
  6. K M Cherian, S Bharati, S G Rao Surgical correction of anomalous origin of the left coronary artery from the pulmonary artery. J Card Surg: 1994, 9(4);386-91 PubMed 7949665
  7. Tiina Ojala, Jukka Salminen, Juha-Matti Happonen, Jaana Pihkala, Eero Jokinen, Heikki Sairanen 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. Interact Cardiovasc Thorac Surg: 2010, 10(1);70-5 PubMed 19808708 | Interact Cardiovasc Thorac Surg.
  8. Tanyanan Tanawuttiwat, Tasma Harindhanavudhi, Dinker Trivedi Anomalous single coronary artery with absent right coronary artery diagnosed with the aid of 64-slice multidetector computed tomographic angiography. Tex Heart Inst J: 2009, 36(4);362-3 PubMed 19693319 PMC2720291
  9. Pallavi Solanki, Christine Gerula, Preet Randhawa, Michael Benz, James Maher, Bunyad Haider, Marc Klapholz, Jack Palmaro, Diane Alfano, Edo Kaluski Right coronary artery anatomical variants: where and how? J Invasive Cardiol: 2010, 22(3);103-6 PubMed 20197575 | J Invasive Cardiol.


Bikram Sharma, Andrew Chang, Kristy Red-Horse Coronary Artery Development: Progenitor Cells and Differentiation Pathways. Annu. Rev. Physiol.: 2017, 79;1-19 PubMed 27959616

Diane E Spicer, Deborah J Henderson, Bill Chaudhry, Timothy J Mohun, Robert H Anderson The anatomy and development of normal and abnormal coronary arteries. Cardiol Young: 2015, 25(8);1493-1503 PubMed 26675596


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See also Category:Heart ILP and Category:Heart

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Cite this page: Hill, M.A. (2018, December 9) Embryology Cardiovascular System - Coronary Circulation Development. Retrieved from

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