Ac-SDKP reverses inflammation and fibrosis in rats with heart failure after myocardial infarction.

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 microg/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)-beta-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.

• Authors: Fang Yang, Xiao-Ping Yang, Yun-He Liu, Jiang Xu, Oscar Cingolani, Nour-Eddine Rhaleb, Oscar A Carretero
• Journal: Hypertension (Dallas, Tex. : 1979) (Hypertension) Vol. 43 Issue 2 Pg. 229-36 (Feb 2004) ISSN: 1524-4563 [Electronic] United States
• PMID: 14691195 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Anti-Inflammatory Agents
• Oligopeptides
• Transforming Growth Factor beta
• Collagen
• goralatide

Topics

• Animals
• Anti-Inflammatory Agents (therapeutic use)
• Blood Pressure (drug effects)
• Cardiac Output, Low (drug therapy, immunology, pathology)
• Cell Movement (drug effects)
• Collagen (analysis)
• Fibrosis
• Heart (drug effects, physiopathology)
• Heart Rate (drug effects)
• Inflammation (drug therapy, prevention & control)
• Macrophages (physiology)
• Male
• Myocardial Infarction (drug therapy, pathology, prevention & control)
• Myocardium (cytology, immunology, pathology)
• Oligopeptides (therapeutic use)
• Rats
• Rats, Inbred Lew
• Transforming Growth Factor beta (analysis)