Hyperinsulinemia and smooth muscle cell proliferation

Area of Science:

• Cardiovascular Biology
• Endocrinology
• Vascular Biology

Background:

• Obesity and diabetes increase atherosclerosis risk, with hyperinsulinemia implicated.
• Insulin stimulates smooth muscle cell (SMC) proliferation in vitro, suggesting a potential atherogenic role.
• Direct in vivo evidence for insulin's growth-promoting effect on SMCs is lacking.

Purpose of the Study:

• To investigate the in vivo effect of acute and chronic hyperinsulinemia on SMC proliferation following arterial injury.
• To determine if insulin, with or without hyperglycemia, influences SMC response to deendothelialization.

Main Methods:

• Animal model: balloon catheter-induced arterial injury (deendothelialization) in rats.
• SMC proliferation assessed by 3H-thymidine incorporation.
• Experimental groups included fasted-refed rats, acarbose-treated rats, and obese Zucker rats.

Main Results:

• Acute hyperinsulinemia, with or without hyperglycemia, did not alter the acute SMC proliferative response to injury.
• In obese Zucker rats, long-term hyperinsulinemia led to significantly reduced decline in SMC proliferation from day 14 to 30 post-injury.
• Obese rats exhibited increased aortic thickness and intimal SMC number 30 days after injury.

Conclusions:

• Acute insulin surges do not appear to directly promote SMC proliferation in response to arterial injury.
• Chronic hyperinsulinemia, characteristic of obesity, promotes long-term SMC proliferation and contributes to arterial wall thickening.
• These findings suggest a role for sustained hyperinsulinemia in the development of atherosclerosis in obese individuals.