Role of carvedilol on energy metabolic reversion and rem odeling of pressure overload-induced left ventricular hypertrophy in rats / 中国病理生理杂志

ABSTRACT

AIM: To study changes of medium chain acyl- Co A dehydrogenase (MCAD), muscle carnitine palmitoyltransferase I (M-CPT-I) and co lligin mRNA/protein expression, to elucidate molecular mechanism of the recapit ulation of fetal energy metabolism and ventricular remodeling and the effects o f carvedilol during the development of pressure overload-induced left ventricula r hypertrophy in rats. METHODS: Male Wistar rats of hypertrophy induced by constrictio n of abdominal aorta (CAA) were randomized into 2 groups (n=12, each group) 4-week group (CAA 4 weeks group) and 12-week carvedilol intervention gro up (CAR group). Additi onal rats (n=12) underwent abdominal cavity incision without ligation to ser ve as age-matched sham operated controls (SH). Hemodynamics, ventricular remodel ing parameters and free fatty acid (FFA) both in blood serum and myocardium we re measured. RT-PCR analysis of the expression of mRNA of M-CPT-I, MCAD and col lagen binding protein (colligin) were investigated. The protein expression of co lligin was analyzed by Western blotting in the experimental animals and sham op eration.RESULTS: LVM/BW and MAP in CAA group were increased more signif icantly than in sham group. There were progressive increases in FAA both in bloo d serum and myocardium in CAA group than in sham group, accompanied with downreg ulation of gene expressions of M-CPT-I and MCAD and colligin mRNA/ protein upre gulation in LV in CAA group, while changes of all of these parameters in CAR gro up were attenuated. CONCLUSIONS: (1) The down-regulated expression of cardiac FAO en zyme genes (M-CPT-I and MCAD) in the hypertrophied heart may be responsible for "the recapitulation of fetal energy metabolism" during the development of pres sure overload-induced left ventricular hypertrophy in rats. (2) Carvedilol atten uates the reversion of the metabolic gene expression back towards fetal type. (3 ) Carvedilol is effective in regressing the left ventricular remodeling by inhi biting colligin protein expression. A molecular mechanism by which carvedilol ma y confer cardioprotective effects in heart failure may be, in part, via preservi ng o f the adult metabolic gene regulation and regressing left ventricular remodeling .