Effects of Ac-Sdkp, a Natural Inhibitor of Hematopoietic Stem Cell Proliferation, on Cardiac Collagen Deposition in Rats with Myocardial Infarction
N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) is a potent natural inhibitor of hematopoietic stem cell proliferation. Recently, it has been shown to inhibit collagen production by cardiac fibroblasts in vitro and collagen content in the left ventricle (LV) of 2K1C hypertensive rats in vivo. We hypothesized that Ac-SDKP may decrease myocardial collagen deposition in rats with myocardial infarction (MI), thereby reducing interstitial fibrosis and improving cardiac function. Lewis inbred rats were subjected to MI by ligating the left anterior descending coronary artery. Either vehicle or Ac-SDKP (400 mg/kg/day, i.p. by osmotic mini-pump) was given 2 months after MI and continued for another 2 months. Systolic blood pressure (SBP) was measured once a month by tail cuff. LV diastolic dimension (LVDd), mass, ejection fraction (EF) and cardiac output (CO) were measured monthly by echocardiography. At the end of the experiment, mean blood pressure (MBP), LV end-diastolic pressure (LVEDP) and dP/dt were determined. Collagen content in the non-infarcted area of the LV was measured by hydroxyproline assay. We found that Ac-SDKP had no effect on most hemodynamic and cardiac functional parameters. However, it significantly decreased collagen content from 26.1 ±2.2 (vehicle) to 14.7 ±4.8 mg/mg dry weight (Ac-SDKP); P < 0.001, associated with an increase in negative dP/dt from 5451.8 ±1240.9 (vehicle) to 7030.3 ±763.2 mm Hg/sec (Ac-SDKP); P < 0.01. These results suggest that Ac-SDKP could be a potent tool to slow down the process of myocardial interstitial fibrosis and improve post-MI diastolic function.