Mechanical Strain Induced Expression of Matrix Metalloproteinase-9 via Stretch-Activated Channels in Rat Abdominal Aortic Dissection

机械应变通过牵张激活通道诱导大鼠腹主动脉夹层中基质金属蛋白酶-9的表达

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Abstract

BACKGROUND The aim of the study was to investigate the expression of matrix metalloproteinase-9 (MMP-9) in rat abdominal aortic dissection (AD) induced by mechanical strain, so as to offer a better understanding of the possible mechanisms of AD. MATERIAL AND METHODS Experimental AD in rats was achieved by the injection of porcine pancreatic elastase. At days 0, 1, 3, 5, 7, 14, 21, and 30 after the establishment of AD model, serum MMP-9 levels were measured by enzyme-linked immunosorbent assay (ELISA). Four groups of vascular rings were stretched in vitro with a mechanical strength of 0 g, 1 g, 3 g, or 5 g for 30 min. Another four groups were pretreated with GdCl3, streptomycin, SN50, and SN50M, followed by stretching with 3 g for 30 min. The messenger RNA and the protein of MMP-9 were analyzed by real-time RT-PCR and Western blotting, and NF-κB p65 was detected by ELISA. RESULTS After the establishment of rat abdominal AD model, the serum MMP-9 levels of AD groups increased significantly. The results showed increased expression of MMP-9 in rat AD vessels stretched with mechanical strength of 1 g, 3 g, and 5 g, but this effect was mostly blocked by Gd Cl3 and streptomycin. The NF-κB activity in aortic rings was activated by stretching with a mechanical strength of 3 g and was blocked by SN50, but not by SN50M. CONCLUSIONS The expression of MMP-9 in serum was increased significantly after rat abdominal AD formation. Mechanical strain induced MMP-9 expression in AD vessels, which was mediated through the activation of the stretch-activated channel-induced NF-κB pathway.

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