Advertisement

Oxidative Stress in Cardiac Valve Development

  • Danielle Huk
  • Joy LincolnEmail author
Chapter
Part of the Oxidative Stress in Applied Basic Research and Clinical Practice book series (OXISTRESS)

Abstract

Formation of the mature valve structures begins during embryogenesis and is initiated with the generation of endocardial cushions following endothelial-to-mesenchymal transformation. As development progresses, endocardial cushions elongate and undergo extensive remodeling of the extracellular matrix by mesenchyme-like valve interstitial cells that reside within the maturing valve primordia. This process is in part, regulated by valve endothelial cells that overlay the valve leaflets and continues until postnatal stages when formation of the stratified valve structure is complete. Many signaling pathways have been shown to regulate valvulogenesis including Transforming Growth Factor β, Vascular endothelial growth factor, Wnt, Notch, and endothelial Nitric Oxide Synthase. In other systems, components of the reactive oxygen species (ROS) serve as secondary messengers to influence activity of these signaling pathways. As this has not been explored in developing valves, this chapter will discuss the potential role of ROS in the embryo and discuss how aberrations in this process could underlie valve pathology after birth.

Keywords

Heart valve Valve endothelial cell Valve interstitial cell Extracellular matrix Endocardial cushion Remodeling Transforming growth factor β Vascular endothelial growth factor Reactive oxygen species Endothelial nitric oxide synthase 

Abbreviations

aVIC

Activated valve interstitial cell

BMP

Bone morphogenetic protein

ECM

Extracellular matrix

EMT

Endothelial-to-mesenchymal transformation

eNOS

Endothelial nitric oxide signaling

eNOS

Endothelial nitric oxide synthase

ERK

Extracellular-signal-regulated kinase

MAPK

Mitogen-activated protein kinase

MMP

Matrix metalloproteinases

NFATc1

Nuclear factor of activated T-cells (c1)

ROS

Reactive oxygen species

SMA

α-Smooth muscle actin

Tgfβ

Transforming Growth Factor β

VEC

Valve endothelial cell

VEGF

Vascular endothelial growth factor

VIC

Valve interstitial cell

References

  1. 1.
    Burton GJ, Jauniaux E. Oxidative stress. Best Pract Res Clin Obstet Gynaecol. 2011;25(3):287–99.PubMedPubMedCentralCrossRefGoogle Scholar
  2. 2.
    Hinton RB, Yutzey KE. Heart valve structure and function in development and disease. Annu Rev Physiol. 2011;73:29–46.PubMedPubMedCentralCrossRefGoogle Scholar
  3. 3.
    Anderson RH, Ho SY, Becker AE. Anatomy of the human atrioventricular junctions revisited. Anat Rec. 2000;260(1):81–91.PubMedCrossRefGoogle Scholar
  4. 4.
    Anderson RH. Clinical anatomy of the aortic root. Heart. 2000;84(6):670–3.PubMedPubMedCentralCrossRefGoogle Scholar
  5. 5.
    Garcia-Martinez V, Sanchez-Quintana D, Hurle JM. Histochemical and ultrastructural changes in the extracellular matrix of the developing chick semilunar heart valves. Acta Anat. 1991;142(1):87–96.PubMedCrossRefGoogle Scholar
  6. 6.
    Gross L, Kugel MA. Topographic anatomy and histology of the valves in the human heart. Am J Pathol. 1931;7(5):445–74.PubMedPubMedCentralGoogle Scholar
  7. 7.
    Tao G, Kotick JD, Lincoln J. Heart valve development, maintenance, and disease: the role of endothelial cells. Curr Top Dev Biol. 2012;100:203–32.PubMedCrossRefGoogle Scholar
  8. 8.
    Balachandran K, Sucosky P, Yoganathan AP. Hemodynamics and mechanobiology of aortic valve inflammation and calcification. Int J Inflamm. 2011;2011:263870.CrossRefGoogle Scholar
  9. 9.
    Lincoln J, Lange AW, Yutzey KE. Hearts and bones: shared regulatory mechanisms in heart valve, cartilage, tendon, and bone development. Dev Biol. 2006;294(2):292–302.PubMedCrossRefGoogle Scholar
  10. 10.
    Icardo JM, Colvee E. Atrioventricular valves of the mouse: III. Collagenous skeleton and myotendinous junction. Anat Rec. 1995;243(3):367–75.PubMedCrossRefGoogle Scholar
  11. 11.
    Kunzelman KS et al. Differential collagen distribution in the mitral valve and its influence on biomechanical behaviour. J Heart Valve Dis. 1993;2(2):236–44.PubMedGoogle Scholar
  12. 12.
    Rabkin-Aikawa E, Mayer Jr JE, Schoen FJ. Heart valve regeneration. Adv Biochem Eng Biotechnol. 2005;94:141–79.PubMedGoogle Scholar
  13. 13.
    Aldous IG et al. Differences in collagen cross-linking between the four valves of the bovine heart: a possible role in adaptation to mechanical fatigue. Am J Physiol Heart Circ Physiol. 2009;296(6):H1898–906.PubMedCrossRefGoogle Scholar
  14. 14.
    Grande-Allen KJ, Liao J. The heterogeneous biomechanics and mechanobiology of the mitral valve: implications for tissue engineering. Curr Cardiol Rep. 2011;13(2):113–20.PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    Sacks MS, David Merryman W, Schmidt DE. On the biomechanics of heart valve function. J Biomech. 2009;42(12):1804–24.PubMedPubMedCentralCrossRefGoogle Scholar
  16. 16.
    Schoen FJ. Evolving concepts of cardiac valve dynamics: the continuum of development, functional structure, pathobiology, and tissue engineering. Circulation. 2008;118(18):1864–80.PubMedCrossRefGoogle Scholar
  17. 17.
    Misfeld M, Sievers HH. Heart valve macro- and microstructure. Phil Trans R Soc Lond B Biol Sci. 2007;362(1484):1421–36.CrossRefGoogle Scholar
  18. 18.
    Liu AC, Gotlieb AI. Characterization of cell motility in single heart valve interstitial cells in vitro. Histol Histopathol. 2007;22(8):873–82.PubMedGoogle Scholar
  19. 19.
    Butcher JT, Nerem RM. Valvular endothelial cells regulate the phenotype of interstitial cells in co-culture: effects of steady shear stress. Tissue Eng. 2006;12(4):905–15.PubMedCrossRefGoogle Scholar
  20. 20.
    Roos CM et al. Transcriptional and phenotypic changes in aorta and aortic valve with aging and MnSOD deficiency in mice. Am J Physiol Heart Circ Physiol. 2013;305(10):H1428–39.PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    Miller JD et al. Dysregulation of antioxidant mechanisms contributes to increased oxidative stress in calcific aortic valvular stenosis in humans. J Am Coll Cardiol. 2008;52(10):843–50.PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    Heistad DD et al. Novel aspects of oxidative stress in cardiovascular diseases. Circ J. 2009;73(2):201–7.PubMedCrossRefGoogle Scholar
  23. 23.
    Perez-Pomares JM, Gonzalez-Rosa JM, Munoz-Chapuli R. Building the vertebrate heart - an evolutionary approach to cardiac development. Int J Dev Biol. 2009;53(8-10):1427–43.PubMedCrossRefGoogle Scholar
  24. 24.
    Person AD, Klewer SE, Runyan RB. Cell biology of cardiac cushion development. Int Rev Cytol. 2005;243:287–335.PubMedCrossRefGoogle Scholar
  25. 25.
    Eisenberg LM, Markwald RR. Molecular regulation of atrioventricular valvuloseptal morphogenesis. Circ Res. 1995;77(1):1–6.PubMedCrossRefGoogle Scholar
  26. 26.
    Combs MD, Yutzey KE. Heart valve development: regulatory networks in development and disease. Circ Res. 2009;105(5):408–21.PubMedPubMedCentralCrossRefGoogle Scholar
  27. 27.
    Lopez-Sanchez C, Garcia-Martinez V. Molecular determinants of cardiac specification. Cardiovasc Res. 2011;91(2):185–95.PubMedCrossRefGoogle Scholar
  28. 28.
    Markwald RR et al. Developmental basis of adult cardiovascular diseases: valvular heart diseases. Ann N Y Acad Sci. 2010;1188:177–83.PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    Schroeder JA et al. Form and function of developing heart valves: coordination by extracellular matrix and growth factor signaling. J Mol Med. 2003;81(7):392–403.PubMedCrossRefGoogle Scholar
  30. 30.
    Lincoln J, Alfieri CM, Yutzey KE. Development of heart valve leaflets and supporting apparatus in chicken and mouse embryos. Dev Dyn. 2004;230(2):239–50.PubMedCrossRefGoogle Scholar
  31. 31.
    de Lange FJ et al. Lineage and morphogenetic analysis of the cardiac valves. Circ Res. 2004;95(6):645–54.PubMedCrossRefGoogle Scholar
  32. 32.
    Lincoln J, Alfieri CM, Yutzey KE. BMP and FGF regulatory pathways control cell lineage diversification of heart valve precursor cells. Dev Biol. 2006;292(2):292–302.PubMedCrossRefGoogle Scholar
  33. 33.
    Wessels A et al. Epicardially derived fibroblasts preferentially contribute to the parietal leaflets of the atrioventricular valves in the murine heart. Dev Biol. 2012;366(2):111–24.PubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    Gittenberger-de Groot AC et al. Epicardium-derived cells contribute a novel population to the myocardial wall and the atrioventricular cushions. Circ Res. 1998;82(10):1043–52.PubMedCrossRefGoogle Scholar
  35. 35.
    Cai CL et al. A myocardial lineage derives from Tbx18 epicardial cells. Nature. 2008;454(7200):104–8.PubMedCrossRefGoogle Scholar
  36. 36.
    Zhou B et al. Epicardial progenitors contribute to the cardiomyocyte lineage in the developing heart. Nature. 2008;454(7200):109–13.PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Lockhart MM et al. The epicardium and the development of the atrioventricular junction in the murine heart. J Dev Biol. 2014;2(1):1–17.PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    Nakamura T, Colbert MC, Robbins J. Neural crest cells retain multipotential characteristics in the developing valves and label the cardiac conduction system. Circ Res. 2006;98(12):1547–54.PubMedCrossRefGoogle Scholar
  39. 39.
    Jiang X et al. Fate of the mammalian cardiac neural crest. Development. 2000;127(8):1607–16.PubMedGoogle Scholar
  40. 40.
    Mjaatvedt CH et al. Normal distribution of melanocytes in the mouse heart. Anat Rec A Discov Mol Cell Evol Biol. 2005;285(2):748–57.PubMedCrossRefGoogle Scholar
  41. 41.
    Hinton Jr RB et al. Extracellular matrix remodeling and organization in developing and diseased aortic valves. Circ Res. 2006;98(11):1431–8.PubMedCrossRefGoogle Scholar
  42. 42.
    Liu Y et al. Nitric oxide synthase-3 promotes embryonic development of atrioventricular valves. PLoS One. 2013;8(10), e77611.PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    El Accaoui RN et al. Aortic valve sclerosis in mice deficient in endothelial nitric oxide synthase. Am J Physiol Heart Circ Physiol. 2014;306(9):H1302–13.PubMedPubMedCentralCrossRefGoogle Scholar
  44. 44.
    Bosse K et al. Endothelial nitric oxide signaling regulates Notch1 in aortic valve disease. J Mol Cell Cardiol. 2013;60:27–35.PubMedPubMedCentralCrossRefGoogle Scholar
  45. 45.
    Gould ST et al. The role of valvular endothelial cell paracrine signaling and matrix elasticity on valvular interstitial cell activation. Biomaterials. 2014;35(11):3596–606.PubMedPubMedCentralCrossRefGoogle Scholar
  46. 46.
    Chang AC et al. Notch initiates the endothelial-to-mesenchymal transition in the atrioventricular canal through autocrine activation of soluble guanylyl cyclase. Dev Cell. 2011;21(2):288–300.PubMedCrossRefGoogle Scholar
  47. 47.
    Timmerman LA et al. Notch promotes epithelial-mesenchymal transition during cardiac development and oncogenic transformation. Genes Dev. 2004;18(1):99–115.PubMedPubMedCentralCrossRefGoogle Scholar
  48. 48.
    Feng Q et al. Development of heart failure and congenital septal defects in mice lacking endothelial nitric oxide synthase. Circulation. 2002;106(7):873–9.PubMedCrossRefGoogle Scholar
  49. 49.
    Shesely EG et al. Elevated blood pressures in mice lacking endothelial nitric oxide synthase. Proc Natl Acad Sci U S A. 1996;93(23):13176–81.PubMedPubMedCentralCrossRefGoogle Scholar
  50. 50.
    Lee TC et al. Abnormal aortic valve development in mice lacking endothelial nitric oxide synthase. Circulation. 2000;101(20):2345–8.PubMedCrossRefGoogle Scholar
  51. 51.
    Sampson N, Berger P, Zenzmaier C. Redox signaling as a therapeutic target to inhibit myofibroblast activation in degenerative fibrotic disease. Biomed Res Int. 2014;2014:131737.PubMedPubMedCentralCrossRefGoogle Scholar
  52. 52.
    Grubisha MJ, DeFranco DB. Local endocrine, paracrine and redox signaling networks impact estrogen and androgen crosstalk in the prostate cancer microenvironment. Steroids. 2013;78(6):538–41.PubMedPubMedCentralCrossRefGoogle Scholar
  53. 53.
    Samarakoon R, Overstreet JM, Higgins PJ. TGF-beta signaling in tissue fibrosis: redox controls, target genes and therapeutic opportunities. Cell Signal. 2013;25(1):264–8.PubMedCrossRefGoogle Scholar
  54. 54.
    Barcellos-Hoff MH. Latency and activation in the control of TGF-beta. J Mammary Gland Biol Neoplasia. 1996;1(4):353–63.CrossRefGoogle Scholar
  55. 55.
    Amarnath S et al. Endogenous TGF-beta activation by reactive oxygen species is key to Foxp3 induction in TCR-stimulated and HIV-1-infected human CD4 + CD25− T cells. Retrovirology. 2007;4:57.PubMedPubMedCentralCrossRefGoogle Scholar
  56. 56.
    Jobling MF et al. Isoform-specific activation of latent transforming growth factor beta (LTGF-beta) by reactive oxygen species. Radiat Res. 2006;166(6):839–48.PubMedCrossRefGoogle Scholar
  57. 57.
    Pociask DA, Sime PJ, Brody AR. Asbestos-derived reactive oxygen species activate TGF-beta1. Lab Invest. 2004;84(8):1013–23.PubMedCrossRefGoogle Scholar
  58. 58.
    Sullivan DE et al. The latent form of TGFbeta(1) is induced by TNFalpha through an ERK specific pathway and is activated by asbestos-derived reactive oxygen species in vitro and in vivo. J Immunotoxicol. 2008;5(2):145–9.PubMedCrossRefGoogle Scholar
  59. 59.
    Vodovotz Y et al. Regulation of transforming growth factor beta1 by nitric oxide. Cancer Res. 1999;59(9):2142–9.PubMedGoogle Scholar
  60. 60.
    Wang H, Kochevar IE. Involvement of UVB-induced reactive oxygen species in TGF-beta biosynthesis and activation in keratinocytes. Free Radic Biol Med. 2005;38(7):890–7.PubMedCrossRefGoogle Scholar
  61. 61.
    Leonarduzzi G et al. The lipid peroxidation end product 4-hydroxy-2,3-nonenal up-regulates transforming growth factor beta1 expression in the macrophage lineage: a link between oxidative injury and fibrosclerosis. FASEB J. 1997;11(11):851–7.PubMedGoogle Scholar
  62. 62.
    Bellocq A et al. Reactive oxygen and nitrogen intermediates increase transforming growth factor-beta1 release from human epithelial alveolar cells through two different mechanisms. Am J Respir Cell Mol Biol. 1999;21(1):128–36.PubMedCrossRefGoogle Scholar
  63. 63.
    Saito K et al. Iron chelation and a free radical scavenger suppress angiotensin II-induced upregulation of TGF-beta1 in the heart. Am J Physiol Heart Circ Physiol. 2005;288(4):H1836–43.PubMedCrossRefGoogle Scholar
  64. 64.
    Shvedova AA et al. Increased accumulation of neutrophils and decreased fibrosis in the lung of NADPH oxidase-deficient C57BL/6 mice exposed to carbon nanotubes. Toxicol Appl Pharmacol. 2008;231(2):235–40.PubMedCrossRefGoogle Scholar
  65. 65.
    Nakajima Y et al. Mechanisms involved in valvuloseptal endocardial cushion formation in early cardiogenesis: roles of transforming growth factor (TGF)-beta and bone morphogenetic protein (BMP). Anat Rec. 2000;258(2):119–27.PubMedCrossRefGoogle Scholar
  66. 66.
    Mercado-Pimentel ME, Runyan RB. Multiple transforming growth factor-beta isoforms and receptors function during epithelial-mesenchymal cell transformation in the embryonic heart. Cells Tissues Organs. 2007;185(1-3):146–56.PubMedCrossRefGoogle Scholar
  67. 67.
    Sanford LP et al. TGFbeta2 knockout mice have multiple developmental defects that are non-overlapping with other TGFbeta knockout phenotypes. Development. 1997;124(13):2659–70.PubMedPubMedCentralGoogle Scholar
  68. 68.
    Bartram U et al. Double-outlet right ventricle and overriding tricuspid valve reflect disturbances of looping, myocardialization, endocardial cushion differentiation, and apoptosis in TGF-beta(2)-knockout mice. Circulation. 2001;103(22):2745–52.PubMedCrossRefGoogle Scholar
  69. 69.
    Sridurongrit S et al. Signaling via the Tgf-beta type I receptor Alk5 in heart development. Dev Biol. 2008;322(1):208–18.PubMedPubMedCentralCrossRefGoogle Scholar
  70. 70.
    Todorovic V et al. Long form of latent TGF-beta binding protein 1 (Ltbp1L) regulates cardiac valve development. Dev Dyn. 2011;240(1):176–87.PubMedPubMedCentralCrossRefGoogle Scholar
  71. 71.
    Lee MW et al. The involvement of reactive oxygen species (ROS) and p38 mitogen-activated protein (MAP) kinase in TRAIL/Apo2L-induced apoptosis. FEBS Lett. 2002;512(1-3):313–8.PubMedCrossRefGoogle Scholar
  72. 72.
    Benhar M et al. Enhanced ROS production in oncogenically transformed cells potentiates c-Jun N-terminal kinase and p38 mitogen-activated protein kinase activation and sensitization to genotoxic stress. Mol Cell Biol. 2001;21(20):6913–26.PubMedPubMedCentralCrossRefGoogle Scholar
  73. 73.
    Krenz M et al. Role of ERK1/2 signaling in congenital valve malformations in Noonan syndrome. Proc Natl Acad Sci U S A. 2008;105(48):18930–5.PubMedPubMedCentralCrossRefGoogle Scholar
  74. 74.
    Son Y et al. Mitogen-activated protein kinases and reactive oxygen species: how can ROS activate MAPK pathways? J Signal Transduct. 2011;2011:792639.PubMedPubMedCentralCrossRefGoogle Scholar
  75. 75.
    Cho HJ et al. Snail is required for transforming growth factor-beta-induced epithelial-mesenchymal transition by activating PI3 kinase/Akt signal pathway. Biochem Biophys Res Commun. 2007;353(2):337–43.PubMedCrossRefGoogle Scholar
  76. 76.
    Romano LA, Runyan RB. Slug is an essential target of TGFbeta2 signaling in the developing chicken heart. Dev Biol. 2000;223(1):91–102.PubMedCrossRefGoogle Scholar
  77. 77.
    Tao G et al. Mmp15 is a direct target of Snai1 during endothelial to mesenchymal transformation and endocardial cushion development. Dev Biol. 2011;359(2):209–21.PubMedPubMedCentralCrossRefGoogle Scholar
  78. 78.
    Zhang A, Dong Z, Yang T. Prostaglandin D2 inhibits TGF-beta1-induced epithelial-to-mesenchymal transition in MDCK cells. Am J Physiol Renal Physiol. 2006;291(6):F1332–42.PubMedCrossRefGoogle Scholar
  79. 79.
    Gorowiec MR et al. Free radical generation induces epithelial-to-mesenchymal transition in lung epithelium via a TGF-beta1-dependent mechanism. Free Radic Biol Med. 2012;52(6):1024–32.PubMedCrossRefGoogle Scholar
  80. 80.
    Rhyu DY et al. Role of reactive oxygen species in TGF-beta1-induced mitogen-activated protein kinase activation and epithelial-mesenchymal transition in renal tubular epithelial cells. J Am Soc Nephrol. 2005;16(3):667–75.PubMedCrossRefGoogle Scholar
  81. 81.
    Kim MC, Cui FJ, Kim Y. Hydrogen peroxide promotes epithelial to mesenchymal transition and stemness in human malignant mesothelioma cells. Asian Pac J Cancer Prev. 2013;14(6):3625–30.PubMedCrossRefGoogle Scholar
  82. 82.
    Chen F et al. Loss of Ikkbeta promotes migration and proliferation of mouse embryo fibroblast cells. J Biol Chem. 2006;281(48):37142–9.PubMedCrossRefGoogle Scholar
  83. 83.
    Dong R et al. Stabilization of snail by HuR in the process of hydrogen peroxide induced cell migration. Biochem Biophys Res Commun. 2007;356(1):318–21.PubMedCrossRefGoogle Scholar
  84. 84.
    Cano A et al. The transcription factor snail controls epithelial-mesenchymal transitions by repressing E-cadherin expression. Nat Cell Biol. 2000;2(2):76–83.PubMedCrossRefGoogle Scholar
  85. 85.
    Lim SO et al. Epigenetic changes induced by reactive oxygen species in hepatocellular carcinoma: methylation of the E-cadherin promoter. Gastroenterology. 2008;135(6):2128–40.e1–8.PubMedCrossRefGoogle Scholar
  86. 86.
    Hurlstone AF et al. The Wnt/beta-catenin pathway regulates cardiac valve formation. Nature. 2003;425(6958):633–7.PubMedCrossRefGoogle Scholar
  87. 87.
    Liebner S et al. Beta-catenin is required for endothelial-mesenchymal transformation during heart cushion development in the mouse. J Cell Biol. 2004;166(3):359–67.PubMedPubMedCentralCrossRefGoogle Scholar
  88. 88.
    Alfieri CM et al. Wnt signaling in heart valve development and osteogenic gene induction. Dev Biol. 2010;338(2):127–35.PubMedCrossRefGoogle Scholar
  89. 89.
    Kajla S et al. A crucial role for Nox 1 in redox-dependent regulation of Wnt-beta-catenin signaling. FASEB J. 2012;26(5):2049–59.PubMedCrossRefGoogle Scholar
  90. 90.
    Wang Y et al. Endocardial to myocardial notch-wnt-bmp axis regulates early heart valve development. PLoS One. 2013;8(4), e60244.PubMedPubMedCentralCrossRefGoogle Scholar
  91. 91.
    Coant N et al. NADPH oxidase 1 modulates WNT and NOTCH1 signaling to control the fate of proliferative progenitor cells in the colon. Mol Cell Biol. 2010;30(11):2636–50.PubMedPubMedCentralCrossRefGoogle Scholar
  92. 92.
    Funato Y, Miki H. Redox regulation of Wnt signalling via nucleoredoxin. Free Radic Res. 2010;44(4):379–88.PubMedCrossRefGoogle Scholar
  93. 93.
    Dor Y et al. A novel role for VEGF in endocardial cushion formation and its potential contribution to congenital heart defects. Development. 2001;128(9):1531–8.PubMedGoogle Scholar
  94. 94.
    Armstrong EJ, Bischoff J. Heart valve development: endothelial cell signaling and differentiation. Circ Res. 2004;95(5):459–70.PubMedPubMedCentralCrossRefGoogle Scholar
  95. 95.
    Ushio-Fukai M et al. Novel role of gp91(phox)-containing NAD(P)H oxidase in vascular endothelial growth factor-induced signaling and angiogenesis. Circ Res. 2002;91(12):1160–7.PubMedCrossRefGoogle Scholar
  96. 96.
    Tojo T et al. Role of gp91phox (Nox2)-containing NAD(P)H oxidase in angiogenesis in response to hindlimb ischemia. Circulation. 2005;111(18):2347–55.PubMedCrossRefGoogle Scholar
  97. 97.
    Stankunas K et al. VEGF signaling has distinct spatiotemporal roles during heart valve development. Dev Biol. 2010;347(2):325–36.PubMedPubMedCentralCrossRefGoogle Scholar
  98. 98.
    Domigan CK, Ziyad S, Iruela-Arispe ML. Canonical and noncanonical vascular endothelial growth factor pathways: new developments in biology and signal transduction. Arterioscler Thromb Vasc Biol. 2015;35(1):30–9.PubMedCrossRefGoogle Scholar
  99. 99.
    Chakraborty S et al. Twist1 promotes heart valve cell proliferation and extracellular matrix gene expression during development in vivo and is expressed in human diseased aortic valves. Dev Biol. 2010;347(1):167–79.PubMedPubMedCentralCrossRefGoogle Scholar
  100. 100.
    Hurle JM et al. Elastic extracellular matrix of the embryonic chick heart: an immunohistological study using laser confocal microscopy. Dev Dyn. 1994;200(4):321–32.PubMedCrossRefGoogle Scholar
  101. 101.
    Rabkin E et al. Activated interstitial myofibroblasts express catabolic enzymes and mediate matrix remodeling in myxomatous heart valves. Circulation. 2001;104(21):2525–32.PubMedCrossRefGoogle Scholar
  102. 102.
    Lincoln J, Yutzey KE. Molecular and developmental mechanisms of congenital heart valve disease. Birth Defects Res A Clin Mol Teratol. 2011;91(6):526–34.PubMedCrossRefGoogle Scholar
  103. 103.
    Aikawa E et al. Human semilunar cardiac valve remodeling by activated cells from fetus to adult: implications for postnatal adaptation, pathology, and tissue engineering. Circulation. 2006;113(10):1344–52.PubMedCrossRefGoogle Scholar
  104. 104.
    Pho M et al. Cofilin is a marker of myofibroblast differentiation in cells from porcine aortic cardiac valves. Am J Physiol Heart Circ Physiol. 2008;294(4):H1767–78.PubMedCrossRefGoogle Scholar
  105. 105.
    Hinz B. Formation and function of the myofibroblast during tissue repair. J Invest Dermatol. 2007;127(3):526–37.PubMedCrossRefGoogle Scholar
  106. 106.
    Forman HJ et al. The chemistry of cell signaling by reactive oxygen and nitrogen species and 4-hydroxynonenal. Arch Biochem Biophys. 2008;477(2):183–95.PubMedPubMedCentralCrossRefGoogle Scholar
  107. 107.
    Cucoranu I et al. NAD(P)H oxidase 4 mediates transforming growth factor-beta1-induced differentiation of cardiac fibroblasts into myofibroblasts. Circ Res. 2005;97(9):900–7.PubMedCrossRefGoogle Scholar
  108. 108.
    Hecker L et al. NADPH oxidase-4 mediates myofibroblast activation and fibrogenic responses to lung injury. Nat Med. 2009;15(9):1077–81.PubMedPubMedCentralCrossRefGoogle Scholar
  109. 109.
    Hagler MA et al. TGF-beta signalling and reactive oxygen species drive fibrosis and matrix remodelling in myxomatous mitral valves. Cardiovasc Res. 2013;99(1):175–84.PubMedPubMedCentralCrossRefGoogle Scholar
  110. 110.
    Liu RM, Gaston Pravia KA. Oxidative stress and glutathione in TGF-beta-mediated fibrogenesis. Free Radic Biol Med. 2010;48(1):1–15.PubMedCrossRefGoogle Scholar
  111. 111.
    Hulin A et al. Emerging pathogenic mechanisms in human myxomatous mitral valve: lessons from past and novel data. Cardiovasc Pathol. 2013;22(4):245–50.PubMedCrossRefGoogle Scholar
  112. 112.
    Miller JD et al. Lowering plasma cholesterol levels halts progression of aortic valve disease in mice. Circulation. 2009;119(20):2693–701.PubMedPubMedCentralCrossRefGoogle Scholar
  113. 113.
    Gao F et al. Extracellular superoxide dismutase inhibits inflammation by preventing oxidative fragmentation of hyaluronan. J Biol Chem. 2008;283(10):6058–66.PubMedCrossRefGoogle Scholar
  114. 114.
    Kliment CR et al. Oxidative stress alters syndecan-1 distribution in lungs with pulmonary fibrosis. J Biol Chem. 2009;284(6):3537–45.PubMedPubMedCentralCrossRefGoogle Scholar
  115. 115.
    Gauldie J et al. Transfer of the active form of transforming growth factor-beta 1 gene to newborn rat lung induces changes consistent with bronchopulmonary dysplasia. Am J Pathol. 2003;163(6):2575–84.PubMedPubMedCentralCrossRefGoogle Scholar
  116. 116.
    Kliment CR, Oury TD. Oxidative stress, extracellular matrix targets, and idiopathic pulmonary fibrosis. Free Radic Biol Med. 2010;49(5):707–17.PubMedCrossRefGoogle Scholar
  117. 117.
    Phillippi JA et al. Altered oxidative stress responses and increased type I collagen expression in bicuspid aortic valve patients. Ann Thorac Surg. 2010;90(6):1893–8.PubMedCrossRefGoogle Scholar
  118. 118.
    Rajamannan NM et al. Atorvastatin inhibits calcification and enhances nitric oxide synthase production in the hypercholesterolaemic aortic valve. Heart. 2005;91(6):806–10.PubMedPubMedCentralCrossRefGoogle Scholar
  119. 119.
    Fu X et al. Hypochlorous acid generated by myeloperoxidase modifies adjacent tryptophan and glycine residues in the catalytic domain of matrix metalloproteinase-7 (matrilysin): an oxidative mechanism for restraining proteolytic activity during inflammation. J Biol Chem. 2003;278(31):28403–9.PubMedCrossRefGoogle Scholar
  120. 120.
    Grote K et al. Mechanical stretch enhances mRNA expression and proenzyme release of matrix metalloproteinase-2 (MMP-2) via NAD(P)H oxidase-derived reactive oxygen species. Circ Res. 2003;92(11):e80–6.PubMedCrossRefGoogle Scholar
  121. 121.
    Pouyet L, Carrier A. Mutant mouse models of oxidative stress. Transgenic Res. 2010;19(2):155–64.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  1. 1.Molecular and Cellular Pharmacology Graduate ProgramLeonard M. Miller School of MedicineMiamiUSA
  2. 2.Center for Cardiovascular Research at Nationwide Children’s Research Institute and The Heart Center at Nationwide Children’s HospitalColumbusUSA
  3. 3.Department of PediatricsThe Ohio State UniversityColumbusUSA

Personalised recommendations