Persistent change in cardiac fibroblast physiology after transient ACE inhibition

K. M. D’Souza, L. A. Biwer, L. Madhavpeddi, P. Ramaiah, W. Shahid, Taben Hale

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Transient angiotensin-converting enzyme (ACE) inhibition induces persistent changes that protect against future nitric oxide synthase (NOS) inhibitorinduced cardiac fibrosis and inflammation. Given the role of fibroblasts in mediating these effects, the present study investigates whether prior ACE inhibition produced persistent changes in cardiac fibroblast physiology. Adult male spontaneously hypertensive rats (SHRs) were treated with vehicle (C+L) or the ACE inhibitor, enalapril (E+L) for 2 wk followed by a 2-wk washout period and a subsequent 7-day challenge with the NOS inhibitor Nω-nitro-L-arginine methyl ester. A third set of untreated SHRs served as controls. At the end of the study period, cardiac fibroblasts were isolated from control, C+L, and E+L left ventricles to assess proliferation rate, collagen expression, and chemokine release in vitro. After 7 days of NOS inhibition, there were areas of myocardial injury but no significant change in collagen deposition in E+L and C+L hearts in vivo. In vitro, cardiac fibroblasts isolated from C+L but not E+L hearts were hyperproliferative, demonstrated increased collagen type I gene expression, and an elevated secretion of the macrophagerecruiting chemokines monocyte chemoattractant protein-1 and granulocyte macrophage-colony stimulating factor. These findings demonstrate that in vivo Nω-nitro-L-arginine methyl ester treatment produces phenotypic changes in fibroblasts that persist in vitro. Moreover, this is the first demonstration that transient ACE inhibition can produce a persistent modification of the cardiac fibroblast phenotype to one that is less inflammatory and fibrogenic. It may be that the cardioprotective effects of ACE inhibition are related in part to beneficial changes in cardiac fibroblast physiology.

Original languageEnglish (US)
Pages (from-to)H1346-H1353
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume309
Issue number8
DOIs
Publication statusPublished - 2015

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Keywords

  • Angiotensin-converting enzyme inhibitor
  • Cardiac fibroblast
  • Collagen
  • Inflammation
  • Proliferation

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)
  • Cardiology and Cardiovascular Medicine

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