SUN-LB127 In Experimental Peripheral Arterial Disease MIR29a Modulation Improves Perfusion Recovery and Muscle Function to a Greater Extent Than ADAM12 Augmentation in Mice With Type 2 Diabetes

摘要

Diabetes Mellitus (DM) is a major risk factor for developing peripheral arterial disease (PAD) and individuals with DM have worse PAD outcomes but the molecular mechanisms involved are poorly understood. We previously identified a disintegrin and metalloproteinase gene 12 (ADAM12) as a key genetic modifier of post-ischemic perfusion recovery in experimental PAD that it is regulated by miR29a through direct interaction. In ischemic hind limbs non-diabetic mice, miR29a expression is downregulated and allows ADAM12 upregulation. However, in ischemic hind limbs of type 2 DM (DM2) mice miR29a expression remains elevated and prevents ADAM12 upregulation. Hence, we hypothesized that inhibition of miR29a or augmenting ADAM12 would improve the impaired perfusion recovery typical of mice with DM2 in experimental PAD. Here, in mice with DM2 we compare the therapeutic effectiveness of miR29a inhibition (miR29aINH) to ADAM12 gene overexpression on perfusion recovery in experimental PAD.