IGF-I and insulin stimulated DNA synthesis (P<0.05) and increased angiotensinogen production (P<0.01) in cultured rat vascular smooth muscle cells, effects that were blocked by captopril.
Do insulin and IGF-I stimulate angiotensinogen production and growth in cultured rat vascular smooth muscle cells?
Insulin and IGF-I stimulate angiotensinogen production and growth in vascular smooth muscle cells, suggesting a mechanism for vascular hypertrophy in insulin resistance.
valor p: p=<0.05
BACKGROUND: Circulating insulin and insulin-like growth factor-I (IGF-I) levels are increased in patients with hypertension and insulin resistance. Since both hormones are known to have cell growth-promoting effects, they may contribute to the progression of vascular hypertrophy in patients with insulin resistance. Insulin-mediated activation of the vascular renin-angiotensin system (RAS) stimulates growth in cultured rat vascular smooth muscle cells (VSMC). OBJECTIVE: In order to evaluate the role of IGF-I-mediated activation of components of the tissue RAS, we examined the effect of IGF-I receptor stimulation on cell proliferation, and production of angiotensinogen in cultured VSMC. STUDY DESIGN: Aortic VSMC were derived from male Sprague-Dawley rats. IGF-I and insulin-mediated DNA synthesis were estimated by 3H-thymidine uptake (3H-TdR) with or without the angiotensin I converting enzyme inhibitor, captopril. Moreover, angiotensinogen released by the cells to the culture medium was determined by radioimmunoassay with or without the anti-IGF-I receptor antibody alphaIR3 or captopril. RESULTS: Both IGF-I and insulin increased 3H-TdR uptake by cultured rat VSMC (P < 0.05). Captopril blocked IGF-I and insulin-mediated 3H-TdR uptake (-34.4 +/- 1.9% and -32.7 +/- 1.8%, P < 0.05, respectively). IGF-I increased the angiotensinogen level in the medium by 30.6 +/- 2.9% (P < 0.01). Insulin also stimulated angiotensinogen synthesis by 26.3 +/- 2.2% (P < 0.01). Captopril and alphaIR3 significantly suppressed angiotensinogen production stimulated by both IGF-I and insulin. CONCLUSIONS: These results indicate that IGF-I as well as insulin stimulates angiotensinogen production and growth in VSMC. Thus, both hormones may independently play a role in progression of the vascular hypertrophy and atherosclerosis in patients with hypertension and insulin resistance through activation of the tissue RAS.
Kamide et al. (Tue,) conducted a other in Vascular hypertrophy in hypertension and insulin resistance. IGF-I and insulin vs. Control (with or without captopril or alphaIR3) was evaluated on DNA synthesis (3H-thymidine uptake) and angiotensinogen production (p=<0.05). IGF-I and insulin stimulated DNA synthesis (P<0.05) and increased angiotensinogen production (P<0.01) in cultured rat vascular smooth muscle cells, effects that were blocked by captopril.