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Genetic and flow anomalies in congenital heart disease

Department of Biomedical Engineering, Oregon Health & Science University, 3303 SW Bond Ave. M/C CH13B, Portland, OR 97239, USA

Congenital heart defects are the most common malformations in humans, affecting approximately 1% of newborn babies. While genetic causes of congenital heart disease have been studied, only less than 20% of human cases are clearly linked to genetic anomalies. The cause for the majority of the cases remains unknown. Heart formation is a finely orchestrated developmental process and slight disruptions of it can lead to severe malformations. Dysregulation of developmental processes leading to heart malformations are caused by genetic anomalies but also environmental factors including blood flow. Intra-cardiac blood flow dynamics plays a significant role regulating heart development and perturbations of blood flow lead to congenital heart defects in animal models. Defects that result from hemodynamic alterations recapitulate those observed in human babies, even those due to genetic anomalies and toxic teratogen exposure. Because important cardiac developmental events, such as valve formation and septation, occur under blood flow conditions while the heart is pumping, blood flow regulation of cardiac formation might be a critical factor determining cardiac phenotype. The contribution of flow to cardiac phenotype, however, is frequently ignored. More research is needed to determine how blood flow influences cardiac development and the extent to which flow may determine cardiac phenotype.
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References

1. Srivastava D, Olson E (2000) A genetic blueprint for cardiac development. Nature 407: 221-226.

2. Rosamond W, Flegal K, Friday G, et al. (2007) Heart disease and stroke statistics-2007 update-A report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 115: E69-E171.

3. Roger VL, Go AS, Lloyd-Jones DM, et al. (2011) Heart disease and stroke statistics--2011 update: a report from the American Heart Association. Circulation 123: E18-E209.    

4. Øyen N, Poulsen G, Boyd HA, et al. (2009) Recurrence of congenital heart defects in families. Circulation 120: 295-301.

5. Roos-Hesselink JW, Kerstjens-Frederikse WS, Meijboom FJ, et al. (2005) Inheritance of congenital heart disease. Neth Heart J 13: 88-91.

6. Mone SM, Gillman MW, Miller TL, et al. (2004) Effects of Environmental Exposures on the Cardiovascular System: Prenatal Period Through Adolescence. Pediatrics 113: 1058-1069.

7. Mills JL, Troendle J, Conley MR, et al. (2010) Maternal obesity and congenital heart defects: a population-based study. Am J Clin Nutr 91: 1543-1549.    

8. Brite J, Laughon SK, Troendle J, et al. (2014) Maternal overweight and obesity and risk of congenital heart defects in offspring. Int J Obes 38: 878-882.    

9. Obler D, Juraszek AL, Smoot LB, et al. (2008) Double outlet right ventricle: aetiologies and associations. J Med Genet 45: 481-497.    

10. Pexieder T (1975) Cell death in the morphogenesis and teratogenesis of the heart. In: Brodal A, Hild W, van Limborgh J et al., editors. Advances in Anatomy, Embryology and Cell Biology. New York: Springer-Verlag.
11. Gluckman PD, Breier BH, Oliver M, et al. (2008) Fetal growth in late gestation—A constrained pattern of growth. Acta Pediatrica 79: 105-110.

12. Gillman MW (2005) Developmental origins of health and disease. N Engl J Med 353: 1848-1850.    

13. Louey S, Thornburg KL (2005) The prenatal environment and later cardiovascular disease. Early Hum Dev 81: 745-751.    

14. Barker DJ, Osmond C, Golding J, et al. (1989) Growth in utero, blood pressure in childhood and adult life, and mortality from cardiovascular disease. Br Med J 298: 564-567.    

15. Leeson CP, Kattenhorn M, Morley M, et al. (2001) Impact of low birth weight and cardiovascular risk factors on endothelial function in early adult life. Circulation 103: 1264-1268.    

16. Hove JR, Koster RW, Forouhar AS, et al. (2003) Intracardiac fluid forces are an essential epigenetic factor for embryonic cardiogenesis. Nature 421: 172-177.

17. Keller BB (1998) Embryonic cardiovascular function, coupling and maturation: a species view. In: Burggren WW, Keller BB, editors. Development of Cardiovascular Systems. Cambridge, MA: University Press.

18. Lucitti JL, Tobita K, Keller BB (2005) Arterial hemodynamics and mechanical properties after circulatory intervention in the chick embryo. J Exp Biol 208: 1877-1885.

19. Clark EB, Rosenquist GC (1978) Spectrum of cardiovascular anomalies following cardiac loop constriction in the chick embryo. Birth Defects Orig Artic Ser 14: 431-442.

20. Sedmera D, Pexieder T, Rychterova V, et al. (1999) Remodeling of chick embryoniv ventricular myoarchitecture under experimentally changed loading conditions. Anat Rec 254: 238-252.

21. Midgett M, Rugonyi S (2014) Congenital heart malformations induced by hemodynamic altering surgical interventions. Front Physiol 5: 287.
22. Barker DJ, Gelow J, Thornburg K, et al. (2010) The early origins of chronic heart failure: impaired placental growth and initiation of insulin resistance in childhood. Eur J Heart Fail 12: 819-825.    

23. Thornburg KL, O'Tierney PF, Louey S (2010) The placenta is a programming agent for cardiovascular disease. Plac Suppl: S54-S59.

24. Scott-Dreschel DE, Rugonyi S, Marks DL, et al. (2013) Hyperglycemia slows embryonic growth and suppresses cell cycle via Cyclin D1 and P21. Diabetes 62: 234-242.

25. Goenezen S, Rennie M, Rugonyi S (2012) Biomechanics of Early cardiac Development. Biomech Model Mechanobiol 11: 1187-1204.    

26. Midgett M, Goenezen S, Rugonyi S (2014) Blood flow dynamics reflect degree of outflow tract banding in Hamburger-Hamilton stage 18 chicken embryos. J R Soc Interface 11: 20140643.    

27. Lindsey SE, Butcher JT, Yalcin HC (2014) Mechanical Regulation of Cardiac Development. Front Physiol 5: 318.

28. Groenendijk BC, Van der Heiden K, Hierck BP, et al. (2007) The role of shear stress on ET-1, KLF2, and NOS-3 expression in the developing cardiovascular system of chicken embryos in a venous ligation model. Physiology 22: 380-389.    

29. Hierck BP, Van der Heiden K, Poelma C, et al. (2008) Fluid shear stress and inner curvature remodeling of the embryonic heart. Choosing the right lane! Scientific World J 8: 212-222.    

30. Poelmann RE, Gittenberger-de Groot AC, Hierck BP (2008) The development of the heart and microcirculation: role of shear stress. Med Biol Eng Comput 46: 479-484.    

31. Nollert G, Fischlein T, Bouterwek S, et al. (1997) Long-term results of total repair of tetralogy of Fallot in adulthood: 35 years follow-up in 104 patients corrected at the age of 18 or older. Thorac Cardiovasc Surg 45: 178-181.    

32. Hoffman J (1995) Incidence of congenital heart disease: I. Postnatal incidence. Pediatr Cardiol 16: 103-113.33. Armstrong EJ, Bischoff J (2004) Heart valve development. Endothelial cell signaling and differentiation. Circ Res 95: 459-470.

34. Nakajima Y, Yamagishi T, Hokari S, et al. (2000) Mechanisms involved in valvuloseptal endocardial cushion formation in early cardiogenesis: roles of transforming growth factor (TGF)-beta and bone morphogenetic protein (BMP). Anat Rec 258: 119-127.

35. Jenkins M, Watanabe M, Rollins A (2012) Longitudinal imaging of heart development with optical coherence tomography. IEEE J Sel Top Quantum Electron 18: 1166-1175.    

36. Liu A, Wang RK, Thornburg KL, et al. (2009) Dynamic variation of hemodynamic shear stress on the walls of developing chick hearts: computational models of the heart outflow tract. Eng Comput 25: 73-86.    

37. Butcher J, McQuinn T, Sedmera D, et al. (2007) Transitions in early embryonic atrioventricular valvular function correspond with changes in cushion biomechanics that are predictable by tissue composition. Circ Res 100: 1503-1511.    

38. Markwald RR, Fitzharris TP, Manasek FJ (1976) Structural development of endocardial cushions. Am J Anat 148: 85-120.

39. Norris RA, Potts JD, Yost MJ, et al. (2009) Periostin promotes a fibroblastic lineage pathway in atrioventricular valve progenitor cells. Dev Dyn 238: 1052-1063.

40. Runyan RB, Markwald RR (1983) Invasion of mesenchyme into three-dimensional collagen gels: a regional and temporal analysis of interaction in embryonic heart tissue. Dev biol 95: 108-114.    

41. Tavares ALP, Mercado-Pimentel ME, Runyan RB, et al. (2006) TGFβ-mediated RhoA expression is necessary for epithelial-mesenchymal transition in the embryonic chick heart. Dev Dyn 235: 1589-1598.    

42. Richards AA, Garg V (2010) Genetics of Congenital Heart Disease. Curr Cardiol Rev 6: 91-97.    

43. Bruneau BG (1997) The developmental genetics of congenital heart disease. Nature 451: 943-948.

44. Bruneau BG (2003) The developing heart and congenital heart defects: a make or break situation. Clinl Genet 63: 252-261.    

45. Schott J-J, Benson DW, Basson CT, et al. (1998) Congenital Heart Disease Caused by Mutations in the Transcription Factor NKX2-5. Science 281: 108-111.

46. Fujita M, Sakabe M, Ioka T, et al. (2016) Pharyngeal arch artery defects and lethal malformations of the aortic arch and its branches in mice deficient for the Hrt1/Hey1 transcription factor. Mech Dev 139: 65-73.

47. Byrd NA, Meyers EN (2005) Loss of Gbx2 results in neural crest cell patterning and pharyngeal arch artery defects in the mouse embryo. Dev Biol 284: 233-245.

48. Fahed AC, Gelb BD, Seidman JG, et al. (2013) Genetics of congenital heart disease: the glass half empty. Circ Res 112: 707-720.

49. Blue GM, Kirk EP, Giannoulatou E, et al. (2014) Targeted Next-Generation Sequencing Identifies Pathogenic Variants in Familial Congenital Heart Disease. J Am Coll Cardiol 64: 2498-2506.

50. Dorn C, Grunert M, Sperling SR (2013) Application of high-throughput sequencing for studying genomic variations in congenital heart disease. Brief Functi Genomics 13: 51-65.

51. Handy DE, Castro R, Loscalzo J (2011) Epigenetic Modifications: Basic Mechanisms and Role in Cardiovascular Disease. Circulation 123: 2145-2156.

52. Granados-Riveron JT, Brook JD (2012) The Impact of Mechanical Forces in Heart Morphogenesis. Circ Cardiovasc Genet 5: 132-142.

53. Eldadah ZA, Hamosh A, Biery NJ, et al. (2001) Familial Tetralogy of Fallot caused by mutation in the jagged1 gene. Hum Mol Genet 10: 163-169.

54. Lin S, Herdt‐Losavio M, Gensburg L, et al. (2009) Maternal asthma, asthma medication use, and the risk of congenital heart defects. Birth Defects Res Part A Clin Mol Teratol 85: 161-168.    

55. Rowland TW, Hubbell JP Jr., Nadas AS (1973) Congenital heart disease in infants of diabetic mothers. J Pediatr 83: 815-820.    

56. Wren C, Birrell G, Hawthorne G (2003) Cardiovascular malformations in infants of diabetic mothers. Heart 89: 1217-1220.    

57. Ferencz C, Rubin JD, McCarter RJ, et al. (1990) Maternal diabetes and cardiovascular malformations: Predominance of double outlet right ventricle and truncus arteriosus. Teratology 41: 319-326.    

58. Park JM, Schmer V, Myers TL (1990) Cardiovascular anomalies associated with prenatal exposure to theophylline. South Med J 83: 1487-1488.
59. Vennemann P, Kiger KT, Lindken R, et al. (2006) In vivo micro particle image velocimetry measurements of blood-plasma in the embryonic avian heart. J Biomech 39: 1191-1200.    

60. Jenkins MW, Adler DC, Gargesha M, et al. (2007) Ultrahigh-speed optical coherence tomography imaging and visualization of the embryonic avian heart using a buffered fourier domain mode locked laser. Opt Express 15: 6251-6267.    

61. Jenkins MW, Peterson L, Gu S, et al. (2010) Measuring hemodynamics in the developing heart tube with four-dimensional gated Doppler optical coherence tomography. J Biomed Opt 15: 066022.    

62. Fujimoto JG (2003) Optical coherence tomography for ultrahigh resolution in vivo imaging. Nat Biotechnol 21: 1361-1367.    

63. Midgett M, Chivukula VK, Dorn C, et al. (2015) Blood flow through the embryonic heart outflow tract during cardiac looping in HH13–HH18 chicken embryos. J R Soc Interface 12: 20150652.    

64. Goodwin RL, Biechler SV, Junor L, et al. (2014) The impact of flow-induced forces on the morphogenesis of the outflow tract. Front Physiol5: 225.

65. Menon V, Eberth J, Goodwin R, et al. (2015) Altered Hemodynamics in the Embryonic Heart Affects Outflow Valve Development. J Cardiovasc Dev Dis 2: 108.    

66. Goodwin RL, Nesbitt T, Price RL, et al. (2005) A three-dimensional model system of valvulogenesis. Dev Dyn 233: 122-129.    

67. Potts JD, Yost MJ, Goodwin RL (2006) Models of cardiovascular development: New approaches are making in vitro en vogue. Curr Cardiol Rev 2: 55-63.    

68. Tan H, Biechler S, Junor L, et al. (2013) Fluid flow forces and rhoA regulate fibrous development of the atrioventricular valves. Dev Biol 374: 345-356.    

Copyright Info: © 2016, Sandra Rugonyi, licensee AIMS Press. This is an open access article distributed under the terms of the Creative Commons Attribution Licese (http://creativecommons.org/licenses/by/4.0)

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