Effect of angiotensin II on primary cardiac fibroblast matrix metalloproteinase activities

Left ventricular dysfunction is associated with reperfusion injury occurring during open-heart surgery. There is an increased secretion of angiotensin II (Ang II) and increased matrix metalloproteinases (MMPs) activities associated with open-heart surgery that may affect the cardiac extracellular matrix (ECM). The goal of this study was to determine the effects of Ang II and selective angiotensin II receptor (AT1-R and AT2-R) blockers on the enzymatic activities of MMPs in primary adult murine cardiac fibroblasts (CF). Our hypothesis is that Ang II, with and without a selective receptor blocker, differentially affects CF MMPs activities. The CF were treated with Ang II (10^-6 M) and doses of AT1-R and AT2-R blockers (losartan and PD123319, respectively) at doses of 10^-7 to 10^-5 M for 48 hours. The Ang II-stimulated CF reduced collagenase activities by only 24% (p=0.004); however, the MMP-2 and MMP-9 gelatinase activities were reduced by 42% and 39%, respectively (p=0.022). The losartan dose dependently increased MMP-2 (p=0.02) and MMP-9 (ns). PD123319 at 10^-5 M significantly reduced MMP-2 and MMP-9 activities compared with the Ang II group (p=0.014 and p=0.02, respectively). The doses of PD123319 at 10^-6 and 10^-7 M increased the MMP-2 and MMP-9 enzymatic activities significantly above the Ang II only group. Thus, Ang II and AT1-R and AT2-R differentially affect the collagenase and gelatinase MMPs activities released by cardiac fibroblasts.