Abstract
Angiotensin II (ANG II) and insulin-like growth factor-1 (IGF-1) are activated early in the development of cardiac hypertrophy. We have shown that angiotensin-converting enzymes (ACE) inhibitors regress eccentric hypertrophy and improve iontropy of the heart. The objective is to evaluate the role of MAPK and PI 3K in the transduction of ANG II and IGF-1 signaling during the development and regression (by ACE inhibitor, Captopril 500mg/l) of eccentric cardiac hypertrophy. Western blot analysis revealed that in hypertrophied heart there is an increase in the activation of Akt (73%), p38 (124%), ERK1 (32%) and ERK2 (41%). In sham, ANG II (10−7M) increased Akt, p38, ERK1 and ERK2 phosphorylation by 37%, 165%, 28% and 73%, respectively. In hypertrophied hearts ANG II mainly increased p38 and ERK2 activation. IGF-1 (10−8M) induced activation of Akt (160%) and p38 (139%) with no change in ERK1 and ERK2 activity in the sham hearts. However in the hypertrophied hearts, IGF-1 induce activation of Akt (125%) and p38 (150%), with a significant activation of ERK2 (100%). Two-week treatment with Captopril did not alter MAPK and PI 3K in the normal hearts. However, in shunt animals it decreased the activation level of Akt, with a minor effect on the activation level of ERK1; concomitant with 50% regression of cardiac hypertrophy. Funded by NIH/NIGMS SCORE S06GM08016-32
Published Version
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