Long-term alcohol consumption increases matrix metalloproteinase-2 activity in rat aorta

Altered degradation of extracellular matrix (ECM) underlies vascular remode ling, a hallmark in the pathogenesis of cardiovascular diseases including h ypertension and aneurysmal dilatation. Although alcohol is recognized as a risk factor for certain cardiovascular-disease states, its role in vascular remodeling has not been completely explored. We studied the effect of chro nic alcohol consumption on upregulation of the enzymatic activity of matrix metalloproteinase-2 (MMP-2) as a possible pathway for large vessel remodel ing. For this purpose, female rats were placed on one of three diets: a mod ified Lieber-DeCarli liquid diet containing 35% ethanol-derived calories, a pair-fed liquid diet with ethanol replaced by isocaloric maltose-dextrin, or a standard rat pellet. Weekly blood alcohol concentration averaged 117+/ -7.9 mg/dl for the alcohol-fed rats. At 2, 4, and 72 weeks, aortas were rem oved and processed for measuring MMPs activity by gelatin zympgraphy. Aorti c extracts from rats on long-term (72 weeks), but not the short-term (2 and 4 weeks), alcohol diets showed increased MMP-2 activity. Furthermore, hist ochemical analysis of the aortas showed distinct disruption of the elastic fibers only in the 72 weeks alcohol-fed rats,: compared to the control anim als. These observations demonstrate:that long-term alcohol consumption up-r egulates MMP-2 activity, which is coincident with the alteration of aortic ECM composition through the degradation of vascular elastin components.