Ac-SDKP Reverses Inflammation and Fibrosis in Rats With Heart Failure After Myocardial Infarction
作者:
Fang Yang,
Xiao-Ping Yang,
Yun-He Liu,
Jiang Xu,
Oscar Cingolani,
Nour-Eddine Rhaleb,
Oscar Carretero,
期刊:
Hypertension: Journal of The American Heart Association
(OVID Available online 2004)
卷期:
Volume 43,
issue 2
页码: 229-236
ISSN:0194-911X
年代: 2004
出版商: OVID
关键词: rat;myocardial infarction;cardiac function;collagen;macrophages;transforming growth factor-&bgr;
数据来源: OVID
摘要:
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 &mgr;g/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)-&bgr;-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.
点击下载:
PDF
(469KB)
返 回