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
.