Effect Of 2-APB In Vivo Intervention On Left Ventricular Hypertrophy Induced By Pressure Overload

Background and objective:Heart failure is an important factor of death in cardiovascular disease and myocardial hypertrophy is the pathological basis in the development of heart failure. To prevent and reverse myocardial hypertrophy is the key to treat heart failure. Transient receptor potential canonical (TRPC) channel in recent years is widely focused for its regulation in the development of heart failure. TRPC1 is thought to be an important part of store-operated Ca2+ channels(SOC) However, little research has studied the effect of using blocker to interfere TRPC1 in vivo. In this research, we build pressure overload model to examine the level of TRPC1 and to investigate the effect of 2-Aminoethoxydiphenyl borate (2-APB) in vivo on left ventricular hypertrophy induced by pressure overload in SD rats.Methods:Eighteen adult male SD rats, weighed 200-250g, were randomly divided in sham-operated group, AAC group and AAC+2-APB group (n=6 in each group).Pressure overload model was created by abdominal aorta constriction (AAC).Rats in AAC+2-APB group were given 2-APB by intraperitoneal injection, once every 2 days,2.5 mg/kg. After administration for 4 weeks, blood pressure, LVMI and LVTDM were measured. The level of TRPC1 mRNA and protein expression were detected by immunohistochemistry, RT-PCR and Western blot.Results:Compared with sham-operated group, LVMI [(2.93±0.23)mg/g vs. (1.82±0.09)mg/g], LVTDM [(20.89±0.79) ?m vs. (13.98±0.16) ?m], the level of TRPC1 mRNA and protein expression were significantly higher in AAC group (P?0.05). Compared with sham-operated group, LVTDM [(16.12±0.50) ?m], the level of TRPC1 mRNA and protein expression were significantly higher in AAC+2-APB group (P<0.05), while LVMI [(1.99±0.09) mg/g] was similar. Compared with AAC group, LVMI, LVTDM, the level of TRPC1 mRNA and protein expression were significantly lower in AAC+2-APB group (P<0.05).Conclusion:TRPC1 was upregulated in left ventricular hypertrophy induced by pressure overload.2-APB in vivo intervention could downregulate the expression of TRPC1, which delayed the progress of left ventricular myocardial hypertrophy to a certain extent.