Effects of aging on pressure-induced MAPK activation in the rat aorta

Abstract

With increasing age, the cardiovascular system experiences substantial alterations in cellular morphology and function. Whilst the factors regulating these changes are unknown, the mitogen-activated protein kinase (MAPK) pathways have emerged as critical components for mediating numerous cellular responses including control of cell growth, differentiation and adaptation. Here we compare the expression, basal activation and the ability of increased pressure to activate the MAPK pathways in adult (6-month-old), aged (30-month-old) and very aged (36-month-old) Fischer 344xBrown Norway F1 hybrid rats. Histochemical analysis demonstrated an age-related increase in tunica media thickness of approximately 11 and 21% in aortae from aged and very aged animals, respectively. Western blot analysis of the MAPK family extracellular signal-regulated kinase (ERK 1/2), p38, and c-Jun NH2 -terminal kinase (JNK) MAPKs showed differential expression and activation among these proteins with age. Expression of ERK 1/2, p38, and JNK were unchanged, slightly increased (10+/-17.5%) or significantly increased (72.3+/-27%), respectively, in very aged aortae. In contrast, basal activation levels of these proteins were reduced (-26.2+/-7.4%), markedly increased (97.0+/-16.8%), and slightly increased (14.4+/-4.5%), respectively, in very aged compared with 6-month rat aortae. An acute increase of aortic intraluminal pressure (200 mmHg) indicated that ERK 1/2 regulation differed from p38 or JNK. Pressure loading-induced phosphorylation of ERK1/2 was unchanged or increased with aging while p38 and JNK phosphorylation was attenuated (P<0.01). These observations confirm previous conclusions that MAPK proteins are regulated mechanically and expand these studies to suggest that MAPK expression and the control of activation are changed with aging.