Aliskiren and valsartan mediate left ventricular remodeling post-myocardial infarction in mice through MMP-9 effects

Trevi A. Ramirez, Rugmani Padmanabhan Iyer, Omid Ghasemi, Elizabeth F. Lopez, Daniel B. Levin, Jianhua Zhang, Rogelio Zamilpa, Youn Min Chou, Yu Fang Jin, Merry L. Lindsey

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

We evaluated whether aliskiren, valsartan, or a combination of both was protective following myocardial infarction (MI) through effects on matrix metalloproteinase (MMP)-9. C57BL/6J wild type (WT, n. = 94) and MMP-9 null (null, n. = 85) mice were divided into 4 groups at 3. h post-MI: saline (S), aliskiren (A; 50. mg/kg/day), valsartan (V; 40. mg/kg/day), or A. +. V and compared to no MI controls at 28. days post-MI. All groups had similar infarct areas, and survival rates were higher in the null mice. The treatments influenced systolic function and hypertrophy index, as well as extracellular matrix (ECM) and inflammatory genes in the remote region, indicating that primary effects were on the viable myocardium. Saline treated WT mice showed increased end systolic and diastolic volumes and hypertrophy index, along with reduced ejection fraction. MMP-9 deletion improved LV function post-MI. Aliskiren attenuated the increase in end systolic volume and hypertrophy index, while valsartan improved end diastolic volumes and aliskiren. +. valsartan improved the hypertrophy index only when MMP-9 was absent. Extracellular matrix and inflammatory gene expression showed distinct patterns among the treatment groups, indicating a divergence in mechanisms of remodeling. This study shows that MMP-9 regulates aliskiren and valsartan effects in mice. These results in mice provide mechanistic insight to help translate these findings to post-MI patients.

Original languageEnglish (US)
Pages (from-to)326-335
Number of pages10
JournalJournal of Molecular and Cellular Cardiology
Volume72
DOIs
StatePublished - Jul 2014

Keywords

  • Aliskiren
  • Extracellular matrix
  • MMP-9
  • Myocardial infarction
  • Remodeling
  • Valsartan

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

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