Folic Acid Attenuates Vascular Dysfunction in Type‐2 Diabetic Mice

Abstract

Diabetes induced hyperhomocysteinemia contributes to endothelial‐myocyte uncoupling and heart failure by activation of matrix metalloproteinase‐9 (MMP‐9). We believe that impairments of arteries in diabetes are associated with endothelial dysfunction mediated by MMP‐9. We hypothesized that folic acid (F) will attenuate vascular dysfunction in type‐2 diabetic mouse (T2D). Diabetes was induced in C57BL/6J mice by feeding a high calorie diet (45% fat). Vascular function (isolated aortic rings) and levels of MMP‐9 (Western blot, and reverse zymography) were determined in thoracic aorta segments of T2D mice and in control (C) mice fed a low calorie diet (10% fat). Mice were regrouped into T2D plus F treatment (T2D+F), and without F treatment (T2D−F). Control groups were also with (C+F) and without (C‐F) treatment. Acetylcholine‐induced relaxation responses were decreased in T2D−F as compared to C‐F, but normalized in T2D+F. The contraction responses to phenylephrine decreased by 40% in aortic rings from T2D−F as compared to C‐F, but were normalized in T2D+F. The sodium nitroprusside‐induced relaxation responses in all groups were not altered. The levels of MMP‐9 were higher in aortic segments from T2D−F as compared to the C‐F, and were significantly reduced in T2D+F. The results suggested that the attenuation of vascular dysfunction in diabetic mice by folic acid is associated with decreased MMP‐9 levels.