Abstract 610: Cardiac and Vascular Hypertrophy Produced by Angiotensin II is Associated with Increases of mTOR/P70S6 Kinases Expression

Abstract

It is fairly well-accepted now that Angiotensin II (Ang II)-infusion produces hypertension and cardiac as well as vascular hypertrophy. In cell culture, the mammalian target of rapamycin (mTOR) and its effector kinase (P70S6) have been shown to increase in cardiomyocytes and smooth muscle cells in response to Ang II and have been suggested to contribute to hypertrophy in these two cell types. The goal of this study was to test the Ang II infusion is associated with increased mTOR and P70S6 expression in vivo . C57BL/6 mice (3 mo of age) were subjected to either sham (control) surgery or surgically implanted with osmotic containing Ang II (1000ng/mit/kg). In mice implanted with Ang II, systolic blood pressure (SBP) was 134±10 mmHg versus 120±5 in control mice. The heart hypertrophy was indicated by heart weight in Ang II group with 30% heavier than the sham controls (mean ± SEM 165.1 ± 5.5 mg versus 126.4 ± 2.9 mg, P<0.01). Quantitative densitometry evaluation of Western Blot showed the ratio 2447 phosphorylated mTOR / total mTOR was significantly elevated in the heart of AngII group with 54% greater than controls (0.51 ± 0.06 versus 0.33 ± 0.01, P < 0.05); and p389-P70S6/total P70S6 was increased by ~75% in Ang II group versus controls (0.07 ± 0.009 to 0.04 ± 0.002 in Ang II-infused and sham mice, respectively, P<0.05). Similarly, p-mTOR/t-mTOR expression increased by ~17% with Ang II treatment (e.g., p-mTOR/t-mTOR expression was 0.69 ± 0.14 to 0.59 ± 0.14 in Ang II-infused and sham mice, respectively, P<0.05); and p-P70S6 / t-P70S6 in Ang II - infused mice was over 50% greater than controls (0.73 ± 0.15 versus 0.46 ± 0.14, P=0.055). Conclusion: mTOR/P70S6 upregulation in the aorta and the heart induced by AngII stimulation indeed happened in vivo and indicates mTOR/P70S6 may play important roles in cardiovascular hypertrophy. Also, they may serve as biomarkers or therapeutics indications. The mechanism of mTOR/P70S6 signaling pathway causing hypertrophy should be further explored.