Expression of Renin-Angiotensin System and Peroxisome Proliferator-Activated Receptors in Alcoholic CardiomyopathyAlcoholism: Clinical and Experimental Research Published Online: 9 Sep 2008
Alcoholic cardiomyopathy (ACM) develops in response to chronic alcohol intake and it is hypothesized that activation of the renin-angiotensin system (RAS) and disorders in energy metabolism may play important roles in its onset. Given that the expression of peroxisome proliferator-activated receptors (PPARα and PPARγ) changes with alterations in cardiac metabolism and myocardial remodeling, this study was designed to test the hypothesis that protein expression of PPARα and PPARγ is correlated with RAS activation in ACM.
Compared with controls, myocardial angiotensin (Ang) I, Ang II, and renin levels were progressively increased at 2, 4, and 6 months of alcohol intake. mRNA expression of renin, angiotensinogen, angiotensin-converting enzyme (ACE), and AT1 was increased at 6 months. Moreover, activated RAS downregulated PPARα and upregulated PPARγ protein expression as ACM progressed. Finally, extracellular signal regulated kinase 1 and 2 (ERK1/2) was shown to play a key role in the regulation of protein expression of PPARα and PPARγ.
These results suggest that RAS is activated during the development of ACM. Moreover, ERK1/2 plays a key role in the regulation of protein expression of PPARα and PPARγ by RAS in ACM.
Request Reprint E-Mail: jingling0451@163.com
_________________________________________________________________
