CORONARY VENOUS SYSTEM DISEASES

Coronary_Venous_System_Diseases

GENETIC AND MOLECULAR PERSPECTIVE

Alkame Akgümüş1 Ahmet Balun2

1Bandırma Onyedi Eylül University, Faculty of Medicine, Department of Cardiology, Balıkesir, Türkiye
2Bandırma Onyedi Eylül University, Faculty of Medicine, Department of Cardiology, Balıkesir, Türkiye

Akgümüş A, Balun A. Genetic and Molecular Perspective. In: Altay S, Akşit E, Kemaloğlu Öz T editor. Coronary Venous System Diseases. 1st ed. Ankara: Türkiye Klinikleri; 2025. p.143-149.

ABSTRACT

In the early stages of embryo development, while the embryo can meet its nutritional needs through diffusion, it has to create a new, effective method to meet its oxygen and nutritional needs and remove waste products from its structure due to its rapid growth in a short time. Therefore, the first system to complete its development in the embryo is the cardiovascular system. The cardiovascular system is not present until the 3rd week of embryological development. Heartbeats begin at the end of the 3rd week of intrauterine life and blood flow becomes observable in the 4th week. The circulatory system is the first system to begin functioning in the embryo and differentiates from the mesenchymal cell pop- ulation originating from the extra-embryonic mesoderm. The embryo is nourished by diffusion from surrounding tissues until the middle of the third week. At the beginning of the third week, angiogenesis formation and primitive placental circulation begin. Blood vessels in the embryo are primarily formed through vasculogenesis, which is the differentiation of precursor cells (angioblasts) into endothelial cells that merge into a vascular network. First, the formation of the vascular plexus occurs in the sub- epicardial area and intramyocardial. Mesenchymal cells known as angioblasts form isolated clusters of angiogenic cells. Small cavities form within the blood islands as the gaps between the cells coalesce. The angioblasts flatten to form endothelial cells. These surround the cavities and form the primitive endothelium. This endothelial cavity line soon coalesces to form networks of endothelial channels.

On the 19th day of development, a pair of vascular structures, the endocardial heart tubes, begin to develop in the cardiogenic region. As the embryo folds laterally on the 20th day, these two heart tubes approach and fuse to form a single tube, the primitive heart tube. The primitive heart tube initially consists solely of endothelium. The cardiac primitive has two poles, the venous and arterial; the caudal venous pole forms the sinus venosus, and the cranial arterial pole forms the bulbus arteriosus.

The complex development of the heart during the embryological period suggests that many genes are involved in this formation. The main molecules important in cardiac embryogenesis are NKX2-5, MEF2C, Hand 1, Hand 2, GATA4 and TBX5. It is thought that these genes also have an effect on the development and diseases of the coronary venous system.

Keywords: Heart; Embryonic Development; Genes; Congenital; Angiogenesis

Referanslar

  1. Anderson RH, Brown NA, Moorman AF. Development and structures of the venous pole of the heart. Dev Dyn. 2006;235(1):2-9. [Crossref]  [PubMed]
  2. Ghandour A, Karuppasamy K, Rajiah P. Congenital Anoma lies of the Superior Vena Cava: Embryological Correlation, Imaging Perspectives, and Clinical Relevance. Can Assoc Radiol J. 2017;68(4):456-462. [Crossref]  [PubMed]
  3. Diatchenko L, Lau YF, Campbell AP, et al. Suppression sub Akgümüş, Balun Genetic and Molecular Perspective tractive hybridization: a method for generating differentially regulated or tissue-specific cDNA probes and libraries. Proc Natl Acad Sci U S A. 1996;93(12):6025-6030. [Crossref]  [PubMed]  [PMC]
  4. van Karnebeek CD, Hennekam RC. Associations between chromosomal anomalies and congenital heart defects: a database search. Am J Med Genet. 1999;84(2):158-166. [Crossref]
  5. Suluba E, Shuwei L, Xia Q, Mwanga A. Congenital heart diseases: genetics, non-inherited risk factors, and signaling pathways. Egypt J Med Hum Genet. 2020;21(11):1-12. [Crossref]
  6. Kodo K, Nishizawa T, Furutani M, et al. Genetic analysis of essential cardiac transcription factors in 256 patients with non-syndromic congenital heart defects. Circ J. 2012;76(7):1703-1711. [Crossref]  [PubMed]
  7. Zhu W, Shiojima I, Hiroi Y, Zou Y, Akazawa H, Mizukami M et al. Functional analyses of three Csx/Nkx-2.5 mutations that cause human congenital heart disease. J Biol Chem. 2000;275(45):35291-6. [Crossref]  [PubMed]
  8. Jiang T, Huang M, Jiang T, et al. Genome-wide compound heterozygosity analysis highlighted 4 novel susceptibility loci for congenital heart disease in Chinese population. Clin Genet. 2018;94(3-4):296-302. [Crossref]  [PubMed]
  9. Hatemi AC, Güleç Ç, Çine N, Vural B, Hatirnaz Ö, Sayitoğlu M. et al. Sequence variations of NKX2-5 and HAND1 genes in patients with atrial isomerism. Anatolian Journal of Cardiology. 2011;11(4):319-28. [Crossref]  [PubMed]
  10. Ellesøe SG, Johansen MM, Bjerre JV, Hjortdal VE, Brunak S, Larsen LA. Familial Atrial Septal Defect and Sudden Cardiac Death: Identification of a Novel NKX2-5 Mutation and a Review of the Literature. Congenit Heart Dis. 2016;11(3):283-290. [Crossref]  [PubMed]  [PMC]
  11. Goldmuntz E, Geiger E, Benson DW. NKX2.5 mutations in patients with tetralogy of fallot. Circulation. 2001;104(21):2565-2568. [Crossref]  [PubMed]
  12. Sepulveda JL, Vlahopoulos S, Iyer D, Belaguli N, Schwartz RJ. Combinatorial expression of GATA4, Nkx2-5, and serum response factor directs early cardiac gene activity. J Biol Chem. 2002;277(28):25775-25782. [Crossref]  [PubMed]
  13. Hiroi Y, Kudoh S, Monzen K, Ikeda Y, Yazaki Y, Nagai R et al. Tbx5 associates with Nkx2-5 and synergistically promotes cardiomyocyte differentiation. Nat Genet. 2001;28:276-80. [Crossref]  [PubMed]
  14. Firulli AB, McFadden DG, Lin Q, Srivastava D, Olson EN. Heart and extra-embryonic mesodermal defects in mouse embryos lacking the bHLH transcription factor Hand1. Nat Genet. 1998;18:266-70. [Crossref]  [PubMed]
  15. Steimle JD, Moskowitz IP. TBX5: a key regulator of heart development. Curr Top Dev Biol. 2017;122:195-221. [Crossref]  [PubMed]  [PMC]
  16. Ríos-Serna LJ, Díaz-Ordoñez L, Candelo E, Pachajoa H. A novel de novo TBX5 mutation in a patient with Holt-Oram syndrome. Appl Clin Genet. 2018;11:157-162. Published 2018 Nov 23. [Crossref]  [PubMed]  [PMC]
  17. Dressen M, Lahm H, Lahm A, Wolf K, Doppler S, Deutsch MA et al. A novel de novo TBX5 mutation in a patient with Holt-Oram syndrome leading to a dramatically reduced biological function. Mol Genet Genomic Med. 2016;4(5):557-67. [Crossref]  [PubMed]  [PMC]
  18. Postma AV, van de Meerakker JB, Mathijssen IB, et al. A gain-of-function TBX5 mutation is associated with atypical Holt-Oram syndrome and paroxysmal atrial fibrillation. Circ Res. 2008;102(11):1433-1442. [Crossref]  [PubMed]
  19. Liu CX, Shen AD, Li XF, et al. Association of TBX5 gene polymorphism with ventricular septal defect in the Chinese Han population. Chin Med J (Engl). 2009;122(1):30-34.
  20. Qiao XH, Wang F, Zhang XL, Huang RT, Xue S, Wang J et al. MEF2C loss-of-function mutation contributes to congenital heart defects. Int J Med Sci. 2017;14(11):1143-53. [Crossref]  [PubMed]  [PMC]
  21. Lu CX, Wang W, Wang Q, Liu XY, Yang YQ. A novel MEF2C loss-of-function mutation associated with congenital double outlet right ventricle. Pediatr Cardiol. 2018;39(4):794-804. [Crossref]  [PubMed]
  22. Nemir M, Pedrazzini T. Functional role of Notch signaling in the developing and postnatal heart. J Mol Cell Cardiol. 2008;45(4):495-504. [Crossref]  [PubMed]
  23. MacGrogan D, Nus M, de la Pompa JL. Notch signaling in cardiac development and disease. Curr Top Dev Biol. 2010;92:333-365. [Crossref]  [PubMed]
  24. D'Amato G, Luxán G, de la Pompa JL. Notch signalling in ventricular chamber development and cardiomyopathy. FEBS J. 2016;283(23):4223-4237. [Crossref]  [PubMed]
  25. Iascone M, Ciccone R, Galletti L, Marchetti D, Seddio F, Lincesso AR et al. Identification of de novo mutations and rare variants in hypoplastic left heart syndrome. Clin Genet. 2012;81(6):542-54. [Crossref]  [PubMed]
  26. Aykan AÇ, Yıldız BŞ. Embriyonun Vasküler Gelişimi. Koşuyolu Heart Journal. 2016;19(2):114-6. [Crossref]
  27. Tomanek RJ. Formation of the coronary vasculature during development. Angiogenesis. 2005;8:273-84. [Crossref]  [PubMed]
  28. Mu H, Ohashi R, Lin P, Yao Q, Chen C. Cellular and molecular mechanisms of coronary vessel development. Vasc Med. 2005;10:37-44. [Crossref]  [PubMed]
  29. Nakajima Y, Imanaka-Yoshida K. New insights into the de Akgümüş, Balun Genetic and Molecular Perspective velopmental mechanisms of coronary vessels and epicardium. Int Rev Cell Mol Biol. 2013;303:263-317. [Crossref]  [PubMed]
  30. Wang HU, Chen ZF, Anderson DJ. Molecular distinction and angiogenic interaction between embryonic arteries and veins revealed by ephrin-B2 and its receptor Eph-B4. Cell. 1998;93(5):741-753. [Crossref]  [PubMed]
  31. Herzog Y, Kalcheim C, Kahane N, Reshef R, Neufeld G. Differential expression of neuropilin-2 in arteries and veins. Mech Dev. 2001;109:115-9. [Crossref]  [PubMed]
  32. Adams RH, Wilkinson GA, Weiss C, Diella F, Gale NW, Deutsch U, et al. Roles of ephrinB ligands and EphB receptors in cardiovascular development demarcation of arterial venous doains, vascular morphogenesis, and sprouting angiogenesis. Genes Dev. 1999;13:295-306. [Crossref]  [PubMed]  [PMC]
  33. Akimoto S, Mitsumata M, Sasaguri T, Yoshida Y. Laminar shear stres inhibits vascular endothelial cell proliferation by inducing cyclin-dependent kinase inhibitor p21(Sdi1/Cip1/ Waf). Circ Res. 2000;86:185-90. [Crossref]  [PubMed]