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Molecular biology of calcific aortic valve disease: towards new pharmacological therapies

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References

  • Rajamannan NM, Evans FJ, Aikawa E, et al. Calcific aortic valve disease: not simply a degenerative process: a review and agenda for research from the National Heart and Lung and Blood Institute Aortic Stenosis Working Group. Executive summary: calcific aortic valve disease-2011 update. Circulation 2011;124(16):1783-91
  • Stewart BF, Siscovick D, Lind BK, et al. Clinical factors associated with calcific aortic valve disease. Cardiovascular Health Study. J Am Coll Cardiol 1997;29(3):630-4
  • Mathieu P, Despres JP, Pibarot P. The ’valvulo-metabolic’ risk in calcific aortic valve disease. Can J Cardiol 2007;23(Suppl B):32B-9B
  • Bosse Y, Miqdad A, Fournier D, et al. Refining molecular pathways leading to calcific aortic valve stenosis by studying gene expression profile of normal and calcified stenotic human aortic valves. Circ Cardiovasc Genet 2009;2(5):489-98
  • Olsson M, Thyberg J, Nilsson J. Presence of oxidized low density lipoprotein in nonrheumatic stenotic aortic valves. Arterioscler Thromb Vasc Biol 1999;19(5):1218-22
  • Cote C, Pibarot P, Despres JP, et al. Association between circulating oxidised low-density lipoprotein and fibrocalcific remodelling of the aortic valve in aortic stenosis. Heart 2008;94(9):1175-80
  • Weiss RM, Ohashi M, Miller JD, et al. Calcific aortic valve stenosis in old hypercholesterolemic mice. Circulation 2006;114(19):2065-9
  • Aikawa E, Aikawa M, Libby P, et al. Arterial and aortic valve calcification abolished by elastolytic cathepsin S deficiency in chronic renal disease. Circulation 2009;119(13):1785-94
  • Teo KK, Corsi DJ, Tam JW, et al. Lipid lowering on progression of mild to moderate aortic stenosis: meta-analysis of the randomized placebo-controlled clinical trials on 2344 patients. Can J Cardiol 2011;27(6):800-8
  • Gerdts E, Rossebo AB, Pedersen TR, et al. Impact of baseline severity of aortic valve stenosis on effect of intensive lipid lowering therapy (from the SEAS study). Am J Cardiol 2010;106(11):1634-9
  • Monzack EL, Masters KS. A time course investigation of the statin paradox among valvular interstitial cell phenotypes. Am J Physiol Heart Circ Physiol 2012;303(7):H903-9
  • Liu AC, Joag VR, Gotlieb AI. The emerging role of valve interstitial cell phenotypes in regulating heart valve pathobiology. Am J Pathol 2007;171(5):1407-18
  • Mathieu P, Pibarot P, Larose E, et al. Visceral obesity and the heart. Int J Biochem Cell Biol 2008;40(5):821-36
  • Mohty D, Pibarot P, Despres JP, et al. Association between plasma LDL particle size, valvular accumulation of oxidized LDL, and inflammation in patients with aortic stenosis. Arterioscler Thromb Vasc Biol 2008;28(1):187-93
  • Capoulade R, Clavel MA, Dumesnil JG, et al. Impact of metabolic syndrome on progression of aortic stenosis: influence of age and statin therapy. J Am Coll Cardiol 2012;60(3):216-23
  • Mahmut A, Boulanger MC, El HD, et al. Elevated expression of lipoprotein-associated phospholipase A2 in calcific aortic valve disease: implications for valve mineralization. J Am Coll Cardiol 2014;63(5):460-9
  • Derbali H, Bosse Y, Cote N, et al. Increased biglycan in aortic valve stenosis leads to the overexpression of phospholipid transfer protein via Toll-like receptor 2. Am J Pathol 2010;176(6):2638-45
  • O’Brien KD, Vuletic S, McDonald TO, et al. Cell-associated and extracellular phospholipid transfer protein in human coronary atherosclerosis. Circulation 2003;108(3):270-4
  • Song R, Zeng Q, Ao L, et al. Biglycan induces the expression of osteogenic factors in human aortic valve interstitial cells via Toll-like receptor-2. Arterioscler Thromb Vasc Biol 2012;32(11):2711-20
  • Osman N, Grande-Allen KJ, Ballinger ML, et al. Smad2-dependent glycosaminoglycan elongation in aortic valve interstitial cells enhances binding of LDL to proteoglycans. Cardiovasc Pathol 2013;22(2):146-55
  • Mahmut A, Boulanger MC, Fournier D, et al. Lipoprotein lipase in aortic valve stenosis is associated with lipid retention and remodelling. Eur J Clin Invest 2013;43(6):570-8
  • Edwards IJ, Goldberg IJ, Parks JS, et al. Lipoprotein lipase enhances the interaction of low density lipoproteins with artery-derived extracellular matrix proteoglycans. J Lipid Res 1993;34(7):1155-63
  • Tsuzuki Y, Nguyen TK, Garud DR, et al. 4-deoxy-4-fluoro-xyloside derivatives as inhibitors of glycosaminoglycan biosynthesis. Bioorg Med Chem Lett 2010;20(24):7269-73
  • Thanassoulis G, Campbell CY, Owens DS, et al. Genetic associations with valvular calcification and aortic stenosis. N Engl J Med 2013;368(6):503-12
  • Arsenault BJ, Boekholdt SM, Dube MP, et al. Lipoprotein(a) levels, genotype and incident aortic valve stenosis: a prospective mendelian randomization study and replication in a case-control cohort. Circ Cardiovasc Genet 2014. [Epub ahead of print]
  • Kamstrup PR, Tybjaerg-Hansen A, Nordestgaard BG. Elevated lipoprotein(a) and risk of aortic valve stenosis in the general population. J Am Coll Cardiol 2014;63(5):470-7
  • Bouchareb R, Boulanger MC, Fournier D, et al. Mechanical strain induces the production of spheroid mineralized microparticles in the aortic valve through a RhoA/ROCK-dependent mechanism. J Mol Cell Cardiol 2014;67:49-59
  • Hung MY, Witztum JL, Tsimikas S. New Therapeutic Targets for Calcific Aortic Valve Stenosis: the Lipoprotein(a)-Lipoprotein-Associated Phospholipase A2-Oxidized Phospholipid Axis. J Am Coll Cardiol 2014;63(5):478-80
  • Wilensky RL, Macphee CH. Lipoprotein-associated phospholipase A2. and atherosclerosis. Curr Opin Lipidol 2009;20(5):415-20
  • White HD, Held C, Stewart R, et al. Darapladib for preventing ischemic events in stable coronary heart disease. N Engl J Med 2014;370:1702-11
  • Merki E, Graham M, Taleb A, et al. Antisense oligonucleotide lowers plasma levels of apolipoprotein (a) and lipoprotein (a) in transgenic mice. J Am Coll Cardiol 2011;57(15):1611-21
  • McKenney JM, Koren MJ, Kereiakes DJ, et al. Safety and efficacy of a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 serine protease, SAR236553/REGN727, in patients with primary hypercholesterolemia receiving ongoing stable atorvastatin therapy. J Am Coll Cardiol 2012;59(25):2344-53
  • Arsenault BJ, Lemieux I, Despres JP, et al. HDL particle size and the risk of coronary heart disease in apparently healthy men and women: the EPIC-Norfolk prospective population study. Atherosclerosis 2009;206(1):276-81
  • Holmes MV, Asselbergs FW, Palmer TM, et al. Mendelian randomization of blood lipids for coronary heart disease. Eur Heart J 2014. [Epub ahead of print]
  • Didonato JA, Aulak K, Huang Y, et al. Site-specific nitration of apolipoprotein A-I at tyrosine 166 is both abundant within human atherosclerotic plaque and dysfunctional. J Biol Chem 2014;289(15):10276-92
  • Audet A, Cote N, Couture C, et al. Amyloid substance within stenotic aortic valves promotes mineralization. Histopathology 2012;61(4):610-19
  • Arsenault BJ, Dube MP, Brodeur MR, et al. Evaluation of links between high-density lipoprotein genetics, functionality, and aortic valve stenosis risk in humans. Arterioscler Thromb Vasc Biol 2014;34(2):457-62
  • Trapeaux J, Busseuil D, Shi Y, et al. Improvement of aortic valve stenosis by ApoA-I mimetic therapy is associated with decreased aortic root and valve remodelling in mice. Br J Pharmacol 2013;169(7):1587-99
  • Busseuil D, Shi Y, Mecteau M, et al. Regression of aortic valve stenosis by ApoA-I mimetic peptide infusions in rabbits. Br J Pharmacol 2008;154(4):765-73
  • Speidl WS, Cimmino G, Ibanez B, et al. Recombinant apolipoprotein A-I Milano rapidly reverses aortic valve stenosis and decreases leaflet inflammation in an experimental rabbit model. Eur Heart J 2010;31(16):2049-57
  • Nagy L, Tontonoz P, Alvarez JG, et al. Oxidized LDL regulates macrophage gene expression through ligand activation of PPARgamma. Cell 1998;93(2):229-40
  • Chu Y, Lund DD, Weiss RM, et al. Pioglitazone attenuates valvular calcification induced by hypercholesterolemia. Arterioscler Thromb Vasc Biol 2013;33(3):523-32
  • Festuccia WT, Laplante M, Brule S, et al. Rosiglitazone-induced heart remodelling is associated with enhanced turnover of myofibrillar protein and mTOR activation. J Mol Cell Cardiol 2009;47(1):85-95
  • Nissen SE, Wolski K. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med 2007;356(24):2457-71
  • Miller JD, Chu Y, Brooks RM, 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
  • El Accaoui RN, Gould ST, Hajj GP, et al. Aortic valve sclerosis in mice deficient in endothelial nitric oxide synthase. Am J Physiol Heart Circ Physiol 2014;306:H1302-H13
  • Rajamannan NM, Subramaniam M, Stock SR, et al. Atorvastatin inhibits calcification and enhances nitric oxide synthase production in the hypercholesterolaemic aortic valve. Heart 2005;91(6):806-10
  • Li H, Forstermann U. Uncoupling of endothelial NO synthase in atherosclerosis and vascular disease. Curr Opin Pharmacol 2013;13(2):161-7
  • Forstermann U, Li H. Therapeutic effect of enhancing endothelial nitric oxide synthase (eNOS) expression and preventing eNOS uncoupling. Br J Pharmacol 2011;164(2):213-23
  • Cote N, Mahmut A, Bosse Y, et al. Inflammation is associated with the remodeling of calcific aortic valve disease. Inflammation 2013;36(3):573-81
  • Yoshioka M, Yuasa S, Matsumura K, et al. Chondromodulin-I maintains cardiac valvular function by preventing angiogenesis. Nat Med 2006;12(10):1151-9
  • Kaden JJ, Dempfle CE, Grobholz R, et al. Inflammatory regulation of extracellular matrix remodeling in calcific aortic valve stenosis. Cardiovasc Pathol 2005;14(2):80-7
  • Edep ME, Shirani J, Wolf P, et al. Matrix metalloproteinase expression in nonrheumatic aortic stenosis. Cardiovasc Pathol 2000;9(5):281-6
  • Sun L, Rajamannan NM, Sucosky P. Defining the role of fluid shear stress in the expression of early signaling markers for calcific aortic valve disease. PLoS One 2013;8(12):e84433
  • Sun L, Chandra S, Sucosky P. Ex vivo evidence for the contribution of hemodynamic shear stress abnormalities to the early pathogenesis of calcific bicuspid aortic valve disease. PLoS One 2012;7(10):e48843
  • Charest A, Pepin A, Shetty R, et al. Distribution of SPARC during neovascularisation of degenerative aortic stenosis. Heart 2006;92(12):1844-9
  • Galeone A, Brunetti G, Oranger A, et al. Aortic valvular interstitial cells apoptosis and calcification are mediated by TNF-related apoptosis-inducing ligand. Int J Cardiol 2013;169(4):296-304
  • Isoda K, Matsuki T, Kondo H, et al. Deficiency of interleukin-1 receptor antagonist induces aortic valve disease in BALB/c mice. Arterioscler Thromb Vasc Biol 2010;30(4):708-15
  • Mahler GJ, Farrar EJ, Butcher JT. Inflammatory cytokines promote mesenchymal transformation in embryonic and adult valve endothelial cells. Arterioscler Thromb Vasc Biol 2013;33(1):121-30
  • El Husseini D, Boulanger MC, Mahmut A, et al. P2Y2 receptor represses IL-6 expression by valve interstitial cells through Akt: implication for calcific aortic valve disease. J Mol Cell Cardiol 2014;72:146-56
  • Tanaka T, Ogata A, Narazaki M. Tocilizumab for the treatment of rheumatoid arthritis. Expert Rev Clin Immunol 2010;6(6):843-54
  • Cote N, Couture C, Pibarot P, et al. Angiotensin receptor blockers are associated with a lower remodelling score of stenotic aortic valves. Eur J Clin Invest 2011;41(11):1172-9
  • Cote N, Pibarot P, Pepin A, et al. Oxidized low-density lipoprotein, angiotensin II and increased waist cirumference are associated with valve inflammation in prehypertensive patients with aortic stenosis. Int J Cardiol 2010;145(3):444-9
  • Campbell SE, Katwa LC. Angiotensin II stimulated expression of transforming growth factor-beta1 in cardiac fibroblasts and myofibroblasts. J Mol Cell Cardiol 1997;29(7):1947-58
  • Zhang M, Wang J, Liu JH, et al. Effects of probucol on angiotensin II-induced BMP-2 expression in human umbilical vein endothelial cells. Mol Med Rep 2013;7(1):177-82
  • O’Brien KD, Probstfield JL, Caulfield MT, et al. Angiotensin-converting enzyme inhibitors and change in aortic valve calcium. Arch Intern Med 2005;165(8):858-62
  • Capoulade R, Clavel MA, Mathieu P, et al. Impact of hypertension and renin-angiotensin system inhibitors in aortic stenosis. Eur J Clin Invest 2013;43(12):1262-72
  • Cote N, Mahmut A, Fournier D, et al. Angiotensin receptor blockers are associated with reduced fibrosis and interleukin-6 expression in calcific aortic valve disease. Pathobiology 2014;81(1):15-24
  • Fujisaka T, Hoshiga M, Hotchi J, et al. Angiotensin II promotes aortic valve thickening independent of elevated blood pressure in apolipoprotein-E deficient mice. Atherosclerosis 2013;226(1):82-7
  • Helske S, Lindstedt KA, Laine M, et al. Induction of local angiotensin II-producing systems in stenotic aortic valves. J Am Coll Cardiol 2004;44(9):1859-66
  • Arishiro K, Hoshiga M, Negoro N, et al. Angiotensin receptor-1 blocker inhibits atherosclerotic changes and endothelial disruption of the aortic valve in hypercholesterolemic rabbits. J Am Coll Cardiol 2007;49(13):1482-9
  • O’Brien KD, Zhao XQ, Shavelle DM, et al. Hemodynamic effects of the angiotensin-converting enzyme inhibitor, ramipril, in patients with mild to moderate aortic stenosis and preserved left ventricular function. J Investig Med 2004;52(3):185-91
  • Garg V, Muth AN, Ransom JF, et al. Mutations in NOTCH1 cause aortic valve disease. Nature 2005;437(7056):270-4
  • Guruharsha KG, Kankel MW, Artavanis-Tsakonas S. The Notch signalling system: recent insights into the complexity of a conserved pathway. Nat Rev Genet 2012;13(9):654-66
  • Nigam V, Srivastava D. Notch1 represses osteogenic pathways in aortic valve cells. J Mol Cell Cardiol 2009;47(6):828-34
  • Nus M, MacGrogan D, Martinez-Poveda B, et al. Diet-induced aortic valve disease in mice haploinsufficient for the Notch pathway effector RBPJK/CSL. Arterioscler Thromb Vasc Biol 2011;31(7):1580-8
  • Ducharme V, Guauque-Olarte S, Gaudreault N, et al. NOTCH1 genetic variants in patients with tricuspid calcific aortic valve stenosis. J Heart Valve Dis 2013;22(2):142-9
  • Rajamannan NM, Subramaniam M, Rickard D, et al. Human aortic valve calcification is associated with an osteoblast phenotype. Circulation 2003;107(17):2181-4
  • Rajamannan NM, Subramaniam M, Caira F, et al. Atorvastatin inhibits hypercholesterolemia-induced calcification in the aortic valves via the Lrp5 receptor pathway. Circulation 2005;112(9 Suppl):I229-34
  • Komiya Y, Habas R. Wnt signal transduction pathways. Organogenesis 2008;4(2):68-75
  • Caira FC, Stock SR, Gleason TG, et al. Human degenerative valve disease is associated with up-regulation of low-density lipoprotein receptor-related protein 5 receptor-mediated bone formation. J Am Coll Cardiol 2006;47(8):1707-12
  • Zhang R, Oyajobi BO, Harris SE, et al. Wnt/beta-catenin signaling activates bone morphogenetic protein 2 expression in osteoblasts. Bone 2013;52(1):145-56
  • Rajamannan NM. The role of Lrp5/6 in cardiac valve disease: experimental hypercholesterolemia in the ApoE-/-/Lrp5-/- mice. J Cell Biochem 2011;112(10):2987-91
  • Deregowski V, Gazzerro E, Priest L, et al. Notch 1 overexpression inhibits osteoblastogenesis by suppressing Wnt/beta-catenin but not bone morphogenetic protein signaling. J Biol Chem 2006;281(10):6203-10
  • Zhang M, Liu X, Zhang X, et al. MicroRNA-30b is a multifunctional regulator of aortic valve interstitial cells. J Thorac Cardiovasc Surg 2014;147(3):1073-80
  • Yanagawa B, Lovren F, Pan Y, et al. miRNA-141 is a novel regulator of BMP-2-mediated calcification in aortic stenosis. J Thorac Cardiovasc Surg 2012;144(1):256-62
  • Hupkes M, Sotoca AM, Hendriks JM, et al. MicroRNA miR-378 promotes BMP2-induced osteogenic differentiation of mesenchymal progenitor cells. BMC Mol Biol 2014;15:1-15
  • Jian B, Narula N, Li QY, et al. Progression of aortic valve stenosis: TGF-beta1 is present in calcified aortic valve cusps and promotes aortic valve interstitial cell calcification via apoptosis. Ann Thorac Surg 2003;75(2):457-65
  • Ankeny RF, Thourani VH, Weiss D, et al. Preferential activation of SMAD1/5/8 on the fibrosa endothelium in calcified human aortic valves-association with low BMP antagonists and SMAD6. PLoS One 2011;6(6):e20969
  • Hutcheson JD, Chen J, Sewell-Loftin MK, et al. Cadherin-11 regulates cell-cell tension necessary for calcific nodule formation by valvular myofibroblasts. Arterioscler Thromb Vasc Biol 2013;33(1):114-20
  • Chen JH, Chen WL, Sider KL, et al. beta-catenin mediates mechanically regulated, transforming growth factor-beta1-induced myofibroblast differentiation of aortic valve interstitial cells. Arterioscler Thromb Vasc Biol 2011;31(3):590-7
  • Hutcheson JD, Ryzhova LM, Setola V, et al. 5-HT(2B) antagonism arrests non-canonical TGF-beta1-induced valvular myofibroblast differentiation. J Mol Cell Cardiol 2012;53(5):707-14
  • Lau WL, Pai A, Moe SM, Giachelli CM. Direct effects of phosphate on vascular cell function. Adv Chronic Kidney Dis 2011;18(2):105-12
  • Linefsky JP, O’Brien KD, Sachs M, et al. Serum phosphate is associated with aortic valve calcification in the Multi-ethnic Study of Atherosclerosis (MESA). Atherosclerosis 2014;233(2):331-7
  • Mathieu P. Pharmacology of ectonucleotidases: relevance for the treatment of cardiovascular disorders. Eur J Pharmacol 2012;696(1-3):1-4
  • Mathieu P, Voisine P, Pepin A, et al. Calcification of human valve interstitial cells is dependent on alkaline phosphatase activity. J Heart Valve Dis 2005;14(3):353-7
  • Cote N, El HD, Pepin A, et al. ATP acts as a survival signal and prevents the mineralization of aortic valve. J Mol Cell Cardiol 2012;52(5):1191-202
  • Okawa A, Nakamura I, Goto S, et al. Mutation in Npps in a mouse model of ossification of the posterior longitudinal ligament of the spine. Nat Genet 1998;19(3):271-3
  • El Husseini D, Boulanger MC, Fournier D, et al. High expression of the Pi-transporter SLC20A1/Pit1 in calcific aortic valve disease promotes mineralization through regulation of Akt-1. PLoS One 2013;8(1):e53393
  • Cote N, El Husseini D, Pepin A, et al. Inhibition of ectonucleotidase with ARL67156 prevents the development of calcific aortic valve disease in warfarin-treated rats. Eur J Pharmacol 2012;689(1-3):139-46

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