Comprehensive transcriptome of proteases and protease inhibitors in vascular cells.

Abstract

Smooth muscle cells, endothelial cells, and macrophages are essential components of the vasculature, of which the homeostatic gene expression participate importantly in the maintenance of vascular wall integrity. The pathogenesis of vascular diseases, such as cerebral ischemia, atherosclerosis, and abdominal aortic aneurysms, often associates with inflammation and altered gene expression, including proteolytic enzymes that play multiple and important roles in extracellular matrix degradation, cell proliferation and migration, and latent enzyme or growth factor activation. Human saphenous vein smooth muscle cells, endothelial cells, and monocyte-derived macrophages from 3 independent donors were stimulated with interleukin 1beta, interferon gamma, tumor necrosis factor alpha, basic fibroblast growth factor, and vascular endothelial growth factor, 5 common proinflammatory mediators often found in diseased human microvessels and macrovessels. Quantitative real-time PCR was used to examine the mRNA levels of 49 proteolytic enzymes and their inhibitors, selected from 4 protease families, in these vascular cells. Although primary cultured cells from different donors may behave differently in response to these proinflammatory cytokines, data from this study revealed a broad view of vascular cell protease expression profiles under inflammatory conditions, critical to studies of inflammation-associated vascular tissue remodeling.