科研之友
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摘要
Mitofusin-2 (Mfin2) suppresses smooth muscle cell proliferation through inhibition of the Ras-extracellular signal-regulated kinases (ERK1/2) pathway. Since the ERK1/2 pathway is implicated in mediating hypertropbic signaling, we studied the changes in Mfn2 in cardiac hypertrophy using in vitro and in vivo models. Pbenylephrime was used to induce hypertrophy in neonatal rat ventricular myocytes (NRVMs). In vivo hypertrophy models included spontaneously hypertensive rats (SHR), pressure-overload hypertrophy by transverse aortic constriction (TAC), hypertrophy of non-infarcted myocardium following myocardial infarction (MI), and cardiomyopathy due to cardiac-restricted overexpression of beta(2)-adrenergic receptors (beta(2)-TG). We determined hypertrophic parameters and analysed expression of atrial natriuretic peptide (ANP) and Mfh2 by real-time PCR. Phosphorylated-ERK1/2 (phospho-ERK) was measured by Western blot. Mfh2 was downregulated in phenylephrine treated NRCMs (by similar to 40%), hypertrophied hearts from SHR (by similar to 80%), mice with TAC (at I and 3 weeks, by similar to 50%), and beta(2)-TG mice (by similar to 20%). However, Mfn2 was not downregulated in hypertrophied hearts with 15 weeks of TAC, nor in hypertrophied non-infarcted myocardium following MI. phospho-ERK1/2 was increased in hypertrophied myocardium at 1 week post-TAC, but not in non-infarcted myocardium after MI, indicating that downregulated Mfn2 may be accompanied by an increase of phospho-ERK1/2. This study shows, for the first time, downregulated Mfn2 expression in hypertrophied hearts, which depends on the etiology and time course of hypertrophy, Further study is required to examine the causal relationship between Mfn2 and cardiac hypertrophy.
- 出版日期2007-5-16
