Age-associated changes in cardiac matrix and integrins

The progressive shift from young age to senescence is characterized by stru ctural and functional changes in the cardiac extracellular matrix (ECM), wh ich supports and aligns myocytes and blood vessels, and maintains myocardia l mass, structure and function. As cardiac function declines with advancing age, ECM collagen and fibronectin influence diastolic stiffness. ECM bindi ng to membrane-bound receptors, or integrins, directly links ECM to cardiac muscle and fibroblast cells, affording it the permissive role to modulate heart function. To better understand the ECM structure-function relationshi p in the old heart, we studied the relative protein content of these ECM pr oteins and integrins across three age groups. Old Balb-c mice (20 months) e xhibit biventricular, cardiac hypertrophy, and greater left ventricular (LV ) collagen, fibronectin, alpha1 and alpha5 integrin protein than middle-age d (12 months) or young (2 months) LV (P<0.05). <beta>1 integrin protein con tent is lower in old LV (P<0.05). These data show that advancing age is ass ociated with greater collagen, fibronectin, <alpha>1 and alpha5 integrin co ntent, suggesting that these matrix proteins undergo coordinated regulation in the aging heart. The differential integrin and ECM protein content sugg ests that there is regulatory signaling to the fibroblasts, which maintain the cardiac ECM. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved .