Simvastatin Preserves Cardiac Function in Genetically Determined Cardiomyopathy

Seena S. Abraham, Juan C. Osorio, Shunichi Homma, Jie Wang, Harshwardhan M. Thaker, James K. Liao, Seema Mital

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

Endothelial dysfunction characterizes heart failure (HF). Simvastatin (Sim) increases endothelial nitric oxide (NO) independent of lipid-lowering. We evaluated the effect of Sim on cardiac function, apoptosis, and NO availability in HF. Five-month-old cardiomyopathic (CM) hamsters were divided into 2 groups: Sim (20 mg/kg, 6 weeks, n = 6) and Untreated (n = 6). Age-matched normal hamsters served as controls (n = 6). Serial echocardiograms were performed to measure LV function. Myocardial apoptosis, eNOS, and capillary density were measured at 6 weeks. Cardiomyopathic hamsters had lower LV shortening fraction (SF) compared with controls (17% vs 59 ± 2%), higher LV end-diastolic volume (30 ± 3 vs 6 ± 2 mL/m2), and lower LV mass/volume ratio (0.5 ± 0.04 vs 0.72 ± 0.02 mg/ml, P < 0.001). During follow-up, SF decreased (9 ± 2%) and LV volume increased (38 ± 1 mL/m2) in untreated hamsters (P < 0.05 from baseline) but did not change significantly in the Sim group (P < 0.05 vs untreated). Myocardial caspase-3 activity was higher and apoptotic nuclear density was lower in Sim compared with untreated CM hamsters (0.072 ± 0.02% vs 0.107 ± 0.03%, P < 0.01). Myocardial capillary density was highest in the Sim group (P < 0.05). eNOS expression was not different between groups. Sim retards the progression of HF in CM hamsters. This may be related to an increase in coronary microvasculature, increase in NO availability, and decreased apoptosis.

Original languageEnglish (US)
Pages (from-to)454-461
Number of pages8
JournalJournal of cardiovascular pharmacology
Volume43
Issue number3
DOIs
StatePublished - Mar 2004

Keywords

  • Angiogenesis
  • Heart failure
  • Nitric oxide
  • Remodeling
  • Statins

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

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