Published Online
on December 22, 2003

A more recent version of this article appeared on February 1, 2004

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Submitted on September 2, 2003
Revised on September 12, 2003

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; and Oscar A. Carretero^*

From the Hypertension and Vascular Research Division (X.-P.Y., Y.-H.L., J.X., O.C., N.-E.R., O.A.C.), Department of Internal Medicine, Henry Ford Hospital, Detroit, Mich, and the Department of Pathology (F.Y.), North China Coal Medicine College, Tangshan, Hebei, People’s Republic of China.

^* To whom correspondence should be addressed. E-mail: ocarret1{at}hfhs.org.

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)--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.

Key words: rat • myocardial infarction • cardiac function • collagen • macrophages • transforming growth factor-

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