Age-associated changes in cardiac matrix and integrins.

The progressive shift from young age to senescence is characterized by structural and functional changes in the cardiac extracellular matrix (ECM), which supports and aligns myocytes and blood vessels, and maintains myocardial mass, structure and function. As cardiac function declines with advancing age, ECM collagen and fibronectin influence diastolic stiffness. ECM binding 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 relationship in the old heart, we studied the relative protein content of these ECM proteins and integrins across three age groups. Old Balb-c mice (20 months) exhibit biventricular, cardiac hypertrophy, and greater left ventricular (LV) collagen, fibronectin, alpha 1 and alpha 5 integrin protein than middle-aged (12 months) or young (2 months) LV (P<0.05). beta1 integrin protein content is lower in old LV (P<0.05). These data show that advancing age is associated with greater collagen, fibronectin, alpha 1 and alpha 5 integrin content, suggesting that these matrix proteins undergo coordinated regulation in the aging heart. The differential integrin and ECM protein content suggests that there is regulatory signaling to the fibroblasts, which maintain the cardiac ECM.