Statins block calcific nodule formation of valvular interstitial cells by inhibiting α-smooth muscle actin expression

Arteriosclerosis, Thrombosis, and Vascular Biology

Volumn 29, Issue 11, 2009, Pages 1950-1957

  Benton, Julie A ^a   Kern, Hanna B ^a   Leinwand, Leslie A ^b   Mariner, Peter D ^b   Anseth, Kristi S ^a,b  

^a University of Colorado at Boulder   (United States)

^b UNIVERSITY OF COLORADO   (United States)

Author keywords

Calcific nodule; Contractility; Myofibroblast; Statin; Valvular interstitial cells

Indexed keywords

ALPHA SMOOTH MUSCLE ACTIN; CALCIUM; PRAVASTATIN;

ANIMAL TISSUE; AORTA VALVE STENOSIS; ARTICLE; CELL AGGREGATION; CONTROLLED STUDY; GENE OVEREXPRESSION; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; SMOOTH MUSCLE CONTRACTILITY; SOFT TISSUE CALCIFICATION;

ACTINS; ANIMALS; AORTIC VALVE; CALCINOSIS; CELL PROLIFERATION; CELLS, CULTURED; FIBROBLASTS; GENE EXPRESSION REGULATION; HYDROXYMETHYLGLUTARYL-COA REDUCTASE INHIBITORS; MUSCLE CONTRACTION; MUSCLE, SMOOTH; PRAVASTATIN; PROBABILITY; REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION; RNA, SMALL INTERFERING; SWINE; TRANSFECTION;

EID: 73949092806     PISSN: 10795642     EISSN: None     Source Type: Journal    
DOI: 10.1161/ATVBAHA.109.195271     Document Type: Article

References (37)

1. Lindroos M, Kupari M, Heikkila J, Tilvis R. Prevalence of aortic-valve abnormalities in the elderly-an echocardiographic study of a random-population sample. J Am Coll Cardiol. 1993;21:1220-1225.
2. Rajamannan NM, Otto CM. Targeted therapy to prevent progression of calcific aortic stenosis. Circulation. 2004;110:1180-1182.
3. Kaden JJ, Bickelhaupt S, Grobholz R, Vahl CE, Hagl S, Brueckmann M, Haase KK, Dempfle CE, Borggrefe M. Expression of bone sialoprotein and bone morphogenetic protein-2 in calcific aortic stenosis. J Heart Valve Dis. 2004;13:560-566.
4. Thubrikar MJ, Aouad J, Nolan SP. Patterns Of calcific deposits in oper-atively excised stenotic or purely regurgitant aortic valves and their relation to mechanical-stress. Am J Cardiol. 1986;58:304-308.
5. Rajamannan NM. Calcific Aortic Stenosis Lessons Learned From Experimental and Clinical Studies. Arterioscler Thromb Vasc Biol. 2009;29: 162-168.
6. Aronow WS, Ahn C, Kronzon I, Goldman ME. Association of coronary risk factors and use of statins with progression of mild valvular aortic stenosis in older persons. Am J Cardiol. 2001;88:693-695. (Pubitemid 32831111)
7. Bellamy MF, Pellikka PA, Klarich KW, Tajik AJ, Enriquez-Sarano M. Association of cholesterol levels, hydroxymethylglutaryl coenzyme-A reductase inhibitor treatment, and progression of aortic stenosis in the community. J Am Coll Cardiol. 2002;40:1723-1730.
8. Novaro GM, Tiong IY, Pearce GL, Lauer MS, Sprecher DL, Griffin BP. Effect of hydroxymethylglutaryl coenzyme A reductase inhibitors on the progression of calcific aortic stenosis. Circulation. 2001;104:2205-2209.
9. Rosenhek R, Rader F, Loho N, Gabriel H, Heger M, Klaar U, Schemper M, Binder T, Maurer G, Baumgartner H. Statins but not angiotensin-converting enzyme inhibitors delay progression of aortic stenosis. Circulation. 2004; 110:1291-1295.
10. Libby P, Aikawa M. Stabilization of atherosclerotic plaques: new mechanisms and clinical targets. Nat Med. 2002;8:1257-1262.
11. Egashira K. Clinical importance of endothelial function in arteriosclerosis and ischemic heart disease. Circulation J. 2002;66:529-533.
12. Rezaie-Majd A, Maca T, Bucek RA, Valent P, Muller MR, Husslein P, Kashanipour A, Minar E, Baghestanian M. Simvastatin reduces expression of cytokines interleukin-6, interleukin-8, and monocyte che-moattractant protein-1 in circulating monocytes from hypercholesterol-emic patients. Arterioscler Thromb Vasc Biol. 2002;22:1194-1199.
13. Shavelle DM, Takasu J, Budoff MJ, Mao SS, Zhao XQ, O'Brien KD. HMG CoA reductase inhibitor (statin) and aortic valve calcium. Lancet. 2002;359:1125-1126.
14. Chan KL, Teo K, Tam J, Dumesnil JG. Rationale, design, and baseline characteristics of a randomized trial to assess the effect of cholesterol lowering on the progression of aortic stenosis: The Aortic Stenosis Progression Observation: Measuring Effects of Rosuvastatin (ASTRONOMER) trial. Am Heart J. 2007;153:925-931.
15. Cowell SJ, Newby DE, Prescott RJ, Bloomfield P, Reid J, Northridge DB, Boon NA. A randomized trial of intensive lipid-lowering therapy in calcific aortic stenosis. N Engl J Med. 2005;352:2389-2397.
16. Rossebo AB, Pedersen TR, Boman K, Brudi P, Chambers JB, Egstrup K, Gerdts E, Gohlke-Barwolf C, Holme I, Kesaniemi YA, Malbecq W, Nienaber CA, Ray S, Skjaerpe T, Wachtell K, Willenheimer R. Intensive lipid lowering with simvastatin and ezetimibe in aortic stenosis. N Engl J Med. 2008;359:1343-1356.
17. Jian B, Narula N, Li QY, Mohler ER, Levy RJ. Progression of aortic valve stenosis: TGF-beta 1 is present in calcified aortic valve cusps and promotes aortic valve interstitial cell calcification via apoptosis. Ann Thorac Surg. 2003;75:457-465.
18. Mohler ER, Chawla MK, Chang AW, Vyavahare N, Levy RJ, Graham L, Gannon FH. Identification and characterization of calcifying valve cells from human and canine aortic valves. J Heart Valve Dis. 1999;8: 254-260.
19. Walker GA, Masters KS, Shah DN, Anseth KS, Leinwand LA. Valvular myofibroblast activation by transforming growth factor-beta-Implications for pathological extracellular matrix remodeling in heart valve disease. Circ Res. 2004;95:253-260.
20. Johnson CM, Hanson MN, Helgeson SC. Porcine cardiac valvular suben-dothelial cells in culture-cell isolation and growth-characteristics. J Mol Cell Cardiol. 1987;19:1185-1193.
21. Rice NA, Leinwand LA. Skeletal myosin heavy chain function in cultured lung myofibroblasts. J Cell Biol. 2003;163:119-129.
22. Cushing MC, Mariner PD, Liao JT, Sims EA, Anseth KS. Fibroblast growth factor represses Smad-mediated myofibroblast activation in aortic valvular interstitial cells. FASEB J. 2008;22:1769-1777.
23. Benton JA, Kern HB, Anseth KS. Substrate properties influence calcification in valvular interstitial cell culture. J Heart Valve Dis. 2008;17: 689-699
24. Pfaffl MW A new mathematical model for relative quantification in real-time RT-PCR. Nucl Acids Res. 2001;29.
25. Clark-Greuel JN, Connolly JM, Sorichillo E, Narula NR, Rapoport HS, Mohler ER, Gorman JH, Gorman RC, Levy RJ. Transforming growth factor-beta 1 mechanisms in aortic valve calcification: Increased alkaline phosphatase and related events. Ann Thoracic Surg. 2007;83:946-953.
26. Meyer-Ter-Vehn T, Sieprath S, Katzenberger B, Gebhardt S, Grehn F, Schlunck G. Contractility as a prerequisite for TGF-beta-induced myofi-broblast transdifferentiation in human tenon fibroblasts. Invest Oph-thalmol Vis Sci. 2006;47:4895-4904. (Pubitemid 46586390)
27. Hinz B, Celetta G, Tomasek JJ, Gabbiani G, Chaponnier C. Alpha-smooth muscle actin expression upregulates fibroblast contractile activity. Mol Biol Cell. 2001;12:2730-2741.
28. Chen JH, Yip CYY, Sone ED, Simmons CA. Identification and characterization of aortic valve mesenchymal progenitor cells with robust osteogenic calcification potential. Am J Pathol. 2009;174:1109-1119.
29. Desmouliere A, Geinoz A, Gabbiani F, Gabbiani G. Transforming growth-factor-beta-1 induces alpha-smooth muscle actin expression in granulation-tissue myofibroblasts and in quiescent and growing cultured fibroblasts. J Cell Biol. 1993;122:103-111.
30. Olsson M, Thyberg J, Nilsson J. Presence of oxidized low density lipoprotein in nonrheumatic stenotic aortic valves. Arterioscler Thromb Vasc Biol. 1999;19:1218-1222.
31. Olsson M, Rosenqvist M, Nilsson J. Expression Of Hla-Dr antigen and smooth-muscle cell-differentiation markers by valvular fibroblasts in degenerative aortic-stenosis. J Am Coll Cardiol. 1994;24:1664-1671.
32. Monzack EL, Gu XX, Masters KS. Efficacy of Simvastatin Treatment of Valvular Interstitial Cells Varies With the Extracellular Environment. Arterioscler Thromb Vasc Biol. 2009;29:246-253.
33. Osman L, Yacoub MH, Latif N, Amrani M, Chester AH. Role of human valve interstitial cells in valve calcification and their response to atorva-statin. Circulation. 2006;114:I547-I552.
34. Wu B, Elmariah S, Kaplan FS, Cheng GJ, Mohler ER. Paradoxical effects of statins on aortic valve myofibroblasts and osteoblasts-Implications for end-stage valvular heart disease. Arterioscler Thromb Vasc Biol. 2005; 25:592-597.
35. Li M, Liu YL, Dutt P, Fanburg BL, Toksoz D. Inhibition of serotonin-induced mitogenesis, migration, and ERK MAPK nuclear translocation in vascular smooth muscle cells by atorvastatin. Am J Physiol-Lung Cell Mol Physiol. 2007;293:L463-L471.
36. Meyer-Ter-Vehn T, Katzenberger B, Han H, Grehn F, Schlunck G. Lovastatin inhibits TGF-beta-induced myofibroblast transdifferentiation in human tenon fibroblasts. Invest Ophthalmol Vis Sci. 2008;49: 3955-3960.
37. Yamashita M, Otsuka F, Mukai T, Otani H, Inagaki K, Miyoshi T, Goto J, Yamamura M, Makino H. Simvastatin antagonizes tumor necrosis factor-a inhibition of bone morphogenetic proteins-2-induced osteoblast differentiation by regulating Smad signaling and Ras/Rho-mitogen-acti-vated protein kinase pathway. J Endocrinol. 2008;196:601-613.