Ac-SDKP Reverses Inflammation and Fibrosis in Rats with Heart Failure after Myocardial Infarction

Fang Yang, Xiao Ping Yang, Yun He Liu, Jiang Xu, Oscar Cingolani, Nour Eddine Rhaleb, Oscar A. Carretero

Research output: Contribution to journalArticlepeer-review

Abstract

Inflammation may play an important role in the pathogenesis of cardiac fibrosis in heart failure (HF) after myocardial infarction (MI). N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) is a naturally occurring antifibrotic peptide whose plasma concentration is increased 4- to 5-fold by angiotensin-converting enzyme inhibitors. We tested the hypothesis that in rats with HF after MI, Ac-SDKP acts as an anti-inflammatory cytokine, preventing and also reversing cardiac fibrosis in the noninfarcted area (reactive fibrosis), and thus affording functional improvement. We found that Ac-SDKP significantly decreased total collagen content in the prevention group from 23.7±0.9 to 15.0±0.7 μg/mg and in the reversal group from 22.6±2.2 to 14.4±1.6 (P<0.01). Interstitial collagen volume fraction and perivascular collagen were likewise significantly reduced. We also found that infiltrating macrophages were reduced from 264.7±8.1 to 170.2±9.2/mm2, p<0.001 (prevention), and from 257.5±9.1 to 153.1±8.5 mm2, P<0.001 (reversal), while transforming growth factor (TGF)-β-positive cells were decreased from 195.6±8.4 to 129.6±5.7/mm2, P<0.01 (prevention), and from 195.6±8.4 to 130.7±10.8/mm2, P<0.01 (reversal). Ac-SDKP did not alter either blood pressure or left ventricular hypertrophy (LVH); however, it depressed systolic cardiac function in the prevention study while having no significant effect in the reversal group. We concluded that Ac-SDKP has an anti-inflammatory effect in HF that may contribute to its antifibrotic effect; however, this decrease in fibrosis without changes in LVH was not accompanied by an improvement in cardiac function.

Original languageEnglish (US)
Pages (from-to)229-236
Number of pages8
JournalHypertension
Volume43
Issue number2 I
DOIs
StatePublished - Feb 2004

Keywords

  • Cardiac function
  • Collagen
  • Macrophages
  • Myocardial infarction
  • Rat
  • Transforming growth factor-β

ASJC Scopus subject areas

  • Internal Medicine

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