The Effects Of Losartan On PKC-ERK₁/ERK₂,P38-MEF2A Signal Pathways And Cardiac Remodeling After Myocardial Infarction In The Rat

Backgroud and Objective The reasons of cardiac remodeling post Myocardial infarction are a series of complex molecular and celluar mechanisms, which contribute to the changes of cardiac structure, function and phenotype. These changes including: myocyte hypertrophy, apoptosis, fibroblast Proliferation,re-expression of fetal gene and protein.Among these changes, myocyte hypertrophy and fibroblast Proliferation are independent risk factors of heart failure, arrhythmia and affect long-term prognostic. It has recently been shown that myocardial local angiotensin II may be one of molecular mechanisms initiating pathologic myocyte hypertrophy and cardiac remodeling. Angiotensin II via coupling angiotensin II type 1 receptor that reside on cadiocyte and fibroblast membrane surface activates PKC, then PKC activating ERK1/ERK2, which transduce the intracellular signal to cell nucleus and modulates genes express in signal transdunction pathway of myocardial hypertrophy. Stretch,angiotensin II and endothelin-1 has been show to activates P38, which as intracellular signal phosphorylate intranuclear transcription factor-myocardial enhance factor 2A (MEF2A). As a sort of DNA-binding protein, phosphorylated MEF2A coupling AT-rich region that exists in muscle-special gene promoter and inducing selective expression of gene and protein. It was shown that stimulation angiotensin II can lead to protein synthesis increased and response hypertrophy in cultured cadiocyte,...