Changes Of Endothlin-1 And GATA Binding Activity And Intervene Of Telmisartan In Cardiomyocyte Of Experimental Rats With Left Ventricular Hypertrophy Induced By Pressure Overloaded

OBJECTIVE Left ventricular hypertrophy(LVH) to result from pressure overloaded condition is a solely dangerous factors that significantly increase morbidity and mortality of cardiovascular diseases. Mechanisms that GATA transcription factors contribute to LVH are remain unknown. Several up-regulated genes including endothelin-1(ET-1) gene, following LVH,are controlled by the transcription factors of GATA. We observed the changes of ET-1 and GATA binding activity in cardiomyocytes from a rat model with LVH induced by partially banding abdominal aortic artery and probed the effect of telmisartan that functions as a angiotensin â…¡ type 1 receptor(AT1R) inhibiter on ET-1. METHODS A rat model of LVH was achieved by partially banding abdominal aortic artery. 24 healthy SD rats were randomly divided into three groups: Sham-operated group(control group,n=8); operated group(LVH group,n=8); operated and telmisartan treatment group(telmisartan group,n=8). In addition, the expression of ET-1 protein, the level of specific combination of ET-1 with GATA and GATA DNA binding activity were determinal by immunohistochemical staining and Gel mobility shift assay respectively. RESULTS Compared with sham-operated control group, SBP, DBP and MBP were significantly enhanced in LVH group(P<0.05). LVMI and DC were higher in LVH group than these in sham-operated contol group(p<0.05). The hypertrophy of cardiomyocytes and the profileration of cardiac interstitial cells were found under optical microscrope. Compared with sham-operated control group, ET-1 protein expression was signidicantly increased in LVH group(p<0.05), ET-1 was positive correlation to LVMI and DC(r=0.895,r=0.899, p<0.01). ET-1 could bind with GATA in Cardiomyocytes. GATA DNA binding activity of cardiomyocytes was enhanced in LVH group(p<0.05). Compared with LVH group, SBP, MBP, LVMI and DC were significantly lowered in LVH telmisartan group. The level of ET-1 protein expressing in cardiomyocyte was decreased by telmisartan(p<0.05). CONCLUSIONS (1)Endothelin-1 expression was increased in cardiomyocytes of the rats with LVH induced by pressure overload, which is positive correlation to LVMI and DC, suggesting that ET-1 plays an important role in LVH.(2) GATA transcription factor can regulate the expression of ET-1 of the heart in normal condition and LVH.(3) GATA transcription factor through increasing the ET-GATA DNA binding activity.can up-regulate the expression of ET-1 resulting in LVH.(4) Telmisartan can reduce the hypertrophy of cardiomyocytes, prevent LVH and reverse heart remodeling by inhibiting ET-GATA DNA binding activity and down-regulating the ET-1 expression.