Transmural pressure induces matrix-degrading activity in porcine arteries ex vivo

Abstract

Extracellular matrix components must be degraded and resynthesized for vascular remodeling to occur. We hypothesized that the hemodynamic environment regulates activity of matrix metalloproteinases (MMPs), the primary agents for in vivo matrix degradation, during vascular remodeling in response to changes in transmural pressure and shear stress. Pathological hemodynamic conditions were reproduced in an ex vivo system in which we maintained porcine carotid arteries for 24 and 48 h. Total levels of MMP-2 and MMP-9 extracted from tissue homogenates and analyzed by SDS-PAGE zymography were stimulated by transmural pressure and were unaffected by shear stress changes. Degradation of two specific gelatinase substrates, gelatin and elastin, increased with increasing pressure, but the degradation was not affected by shear stress changes in tissue specimens analyzed using in situ zymography (gelatin) and fluorescent measurement of endogenous elastin degradation (elastin). Our results suggest that transmural pressure activates at least two members of the MMP family and that activity of these enzymes is accompanied by degradation of matrix components, effects that may be implicated in hypertensive vascular remodeling.