Simvastatin rescues rats from fatal pulmonary hypertension by inducing apoptosis of neointimal smooth muscle cells

Circulation

Volumn 108, Issue 13, 2003, Pages 1640-1645

  Nishimura, Toshihiko ^a   Vaszar, Laszlo T ^a   Faul, John L ^a   Zhao, Guohua ^a   Berry, Gerald J ^b   Shi, Lingfang ^a   Qiu, Daoming ^a   Benson, Gail ^a   Pearl, Ronald G ^a   Kao, Peter N ^a  

^a STANFORD UNIVERSITY MEDICAL CENTER   (United States)

^b STANFORD UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Pulmonary heart disease; Remodeling; Statins; Vasculature

Indexed keywords

BONE MORPHOGENETIC PROTEIN; BONE MORPHOGENETIC PROTEIN 1A; GENE PRODUCT; MONOCROTALINE; NITRIC OXIDE SYNTHASE; PROTEIN FOS; PROTEIN P27; SIMVASTATIN; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; APOPTOSIS; ARTICLE; CELL CYCLE; CELL PROLIFERATION; CONTROLLED STUDY; DEATH; DRUG EFFICACY; DRUG MECHANISM; GENE EXPRESSION REGULATION; HEART RIGHT VENTRICLE HYPERTROPHY; INTIMA; NONHUMAN; PRIORITY JOURNAL; PULMONARY HYPERTENSION; RAT; SMOOTH MUSCLE FIBER; SURVIVAL; TRANSCRIPTION REGULATION; TREATMENT OUTCOME;

ANIMALS; APOPTOSIS; ARTERIAL OCCLUSIVE DISEASES; CELL DIVISION; GENE EXPRESSION PROFILING; HEMODYNAMIC PROCESSES; HYDROXYMETHYLGLUTARYL-COA REDUCTASE INHIBITORS; HYPERTENSION, PULMONARY; HYPERTROPHY; HYPERTROPHY, RIGHT VENTRICULAR; LUNG; MUSCLE, SMOOTH, VASCULAR; PULMONARY ARTERY; RATS; SIMVASTATIN; SURVIVAL ANALYSIS; TUNICA INTIMA;

EID: 0141730236     PISSN: 00097322     EISSN: None     Source Type: Journal    
DOI: 10.1161/01.CIR.0000087592.47401.37     Document Type: Article

References (29)

1. Carmeliet P. Mechanisms of angiogenesis and arteriogenesis. Nat Med. 2000;6:389-395.
2. Fishman AP, Fishman MC, Freeman BA, et al. Mechanisms of proliferative and obliterative vascular diseases: insights from the pulmonary and systemic circulations. NHLBI Workshop summary. Am J Respir Crit Care Med. 1998;158:670-674.
3. Tuder RM, Voelkel NF. Pulmonary hypertension and inflammation. J Lab Clin Med. 1998;132:16-24.
4. Yi ES, Kim H, Ahn H, et al. Distribution of obstructive intimal lesions and their cellular phenotypes in chronic pulmonary hypertension: a morphometric and immunohistochemical study. Am J Respir Crit Care Med. 2000;162:1577-1586.
5. Deng Z, Morse JH, Slager SL, et al. Familial primary pulmonary hypertension (gene PPH1) is caused by mutations in the bone morphogenetic protein receptor-II gene. Am J Hum Genet. 2000;67:737-744.
6. Lane KB, Machado RD, Pauciulo MW, et al. Heterozygous germline mutations in BMPR2, encoding a TGF-beta receptor, cause familial primary pulmonary hypertension. The International PPH Consortium. Nat Genet. 2000;26:81-84.
7. Du L, Sullivan CC, Chu B, et al. Signaling molecules in nonfamilial pulmonary hypertension. N Engl J Med. 2003;348:500-509.
8. Faul JL, Nishimura T, Berry GJ, et al. Triptolide attenuates pulmonary arterial hypertension and neointimal formation in rats. Am J Respir Crit Care Med. 2000;162:2252-2258.
9. Nishimura T, Faul JL, Berry GJ, et al. 40-O-(2-Hydroxyethyl)-rapamycin attenuates pulmonary arterial hypertension and neointimal formation in rats. Am J Respir Crit Care Med. 2001;163:498-502.
10. Newman JH, Lane KB. Hypertensive pulmonary vascular disease: dawn of the age of prevention? Am J Respir Crit Care Med. 2000;162: 2020-2021.
11. Nishimura T, Faul JL, Berry GJ, et al. Simvastatin attenuates smooth muscle neointimal proliferation and pulmonary hypertension in rats. Am J Respir Crit Care Med. 2002;166:1403-1408.
12. Maron DJ, Fazio S, Linton MF. Current perspectives on statins. Circulation. 2000;101:207-213.
13. Kwak B, Mulhaupt F, Myit S, et al. Statins as a newly recognized type of immunomodulator. Nat Med. 2000;6:1399-1402.
14. Bustos C, Hernandez-Presa MA, Ortego M, et al. HMG-CoA reductase inhibition by atorvastatin reduces neointimal inflammation in a rabbit model of atherosclerosis. J Am Coll Cardiol. 1998;32:2057-2064.
15. Soma MR, Donetti E, Parolini C, et al. HMG CoA reductase inhibitors: in vivo effects on carotid intimal thickening in normocholesterolemic rabbits. Arterioscler Thromb. 1993;13:571-578.
16. Laufs U, Marra D, Node K, et al. 3-Hydroxy-3-methylglutaryl-CoA reductase inhibitors attenuate vascular smooth muscle proliferation by preventing rho GTPase-induced down-regulation of p27(Kip1). J Biol Chem. 1999;274:21926-21931.
17. Indolfi C, Cioppa A, Stabile E, et al. Effects of hydroxymethylglutaryl coenzyme A reductase inhibitor simvastatin on smooth muscle cell proliferation in vitro and neointimal formation in vivo after vascular injury. J Am Coll Cardiol. 2000;35:214-221.
18. Laufs U, Fata VL, Liao JK. Inhibition of 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase blocks hypoxia-mediated down-regulation of endothelial nitric oxide synthase. J Biol Chem. 1997;272:31725-31729.
19. Kureishi Y, Luo Z, Shiojima I, et al. The HMG-CoA reductase inhibitor simvastatin activates the protein kinase Akt and promotes angiogenesis in normocholesterolemic animals. Nat Med. 2000;6:1004-1010.
20. Dysvik B, Jonassen I. J-express: exploring gene expression data using Java. Bioinformatics. 2001;17:369-370.
21. Lame MW, Jones AD, Wilson DW, et al. Protein targets of monocrotaline pyrrole in pulmonary artery endothelial cells. J Biol Chem. 2000;275: 29091-29099.
22. Okada K, Tanaka Y, Bernstein M, et al. Pulmonary hemodynamics modify the rat pulmonary artery response to injury: a neointimal model of pulmonary hypertension. Am J Pathol. 1997;151:1019-1025.
23. Nishimura T, Faul JL, Berry GJ, et al. Effect of a surgical aortocaval fistula on monocrotaline-induced pulmonary hypertension. Crit Care Med. 2003;31:1213-1218.
24. Indolfi C, Di Lorenzo E, Perrino C, et al. Hydroxymethylglutaryl coenzyme A reductase inhibitor simvastatin prevents cardiac hypertrophy induced by pressure overload and inhibits p21ras activation. Circulation. 2002;106:2118-2124.
25. Patel R, Nagueh SF, Tsybouleva N, et al. Simvastatin induces regression of cardiac hypertrophy and fibrosis and improves cardiac function in a transgenic rabbit model of human hypertrophic cardiomyopathy. Circulation. 2001;104:317-324.
26. Buemi M, Allegra A, Senatore M, et al. Pro-apoptotic effect of fluvastatin on human smooth muscle cells. Eur J Pharmacol. 1999;370:201-203.
27. Blanco-Colio LM, Villa A, Ortego M, et al. 3-Hydroxy-3-methyl-glutaryl coenzyme A reductase inhibitors, atorvastatin and simvastatin, induce apoptosis of vascular smooth muscle cells by downregulation of Bcl-2 expression and Rho A prenylation. Atherosclerosis. 2002;161:17-26.
28. Vrtovsnik F, Couette S, Prie D, et al. Lovastatin-induced inhibition of renal epithelial tubular cell proliferation involves a p21ras activated, AP-1-dependent pathway. Kidney Int. 1997;52:1016-1027.
29. Kreuzer J, Watson L, Herdegen T, et al. Effects of HMG-CoA reductase inhibition on PDGF- and angiotensin II-mediated signal transduction: suppression of c-Jun and c-Fos in human smooth muscle cells in vitro. Eur J Med Res. 1999;4:135-143.