Abstract 9895: Metformin Attenuates Atherosclerosis and Vascular Aging Beyond Glycemic Control
Background: Cardiovascular disease due to atherosclerosis, the main cause of morbidity and mortality in most of the world, can be exacerbated by other age-related changes in blood vessels, including arterial stiffness mediated by angiotensin II (Ang II). Thus, strategies that can target atherosclerosis and vascular aging concomitantly are of special interest. Metformin, the first line medication for type 2 diabetes, was shown to attenuate all-cause mortality and myocardial infarction compared with other standard diabetes medications, suggesting that metformin has protective effects in the cardiovascular system beyond its glucose control activities. However, the exact mechanism(s) of action for metformin that are beyond its antihyperglycemic effects are still unknown.
Methods and Results: We found that metformin even at concentrations as low as 20 μM can decrease Ang II-induced senescence of vascular smooth muscle cells. Using the ApoE-Knockout mice, we further tested whether metformin can diminish the progression of atherosclerosis and vascular aging and in response to Ang II treatment or high fat diet (HFD). We found that both Ang II induced hypertension and vascular aging were almost completely abolished by metformin treatment. Moreover, metformin treated animals had significantly less atherosclerotic plaque area compared with control groups. Similar vasculoprotective effects were observed when metformin was given to the mice fed HFD (Fig. 1). However, the vasculoprotective findings in both models were not accompanied by significant differences in blood glucose or cholesterol levels. Based on our ongoing studies, these effects of metformin could be explained, at least in part, by its role in modulation of the mTOR pathway that plays a major role in response to nutrition status.
Conclusion: Metformin can be useful as a primary or secondary preventive therapy for patients at risk of suffering cardiovascular disease even in the absence of diabetes.
- © 2013 by American Heart Association, Inc.