Journal
HYPERTENSION
Volume 43, Issue 2, Pages 229-236Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/01.HYP.0000107777.91185.89
Keywords
rat; myocardial infarction; cardiac function; collagen; macrophages; transforming growth factor-beta
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Funding
- NHLBI NIH HHS [R01 HL071806-03, R01 HL071806-01, R01 HL071806, HL28982, R01 HL071806-02, R01 HL071806-04, P01 HL028982] Funding Source: Medline
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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 mug/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/ mm(2), P < 0.001 (prevention), and from 257.5 +/- 9.1 to 153.1 +/- 8.5 mm(2), P < 0.001 (reversal), while transforming growth factor (TGF)-beta-positive cells were decreased from 195.6 +/- 8.4 to 129.6 +/- 5.7/ mm(2), P < 0.01 (prevention), and from 195.6 +/- 8.4 to 130.7 +/- 10.8/ mm(2), 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.
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