Abstract P245: Therapeutic Effects Of Mir-29b-Chitosan On Hypertension And Diabetic Complications

MicroRNA miR-29 promotes endothelial function in human arterioles in part by targeting LYPLA1 and increasing nitric oxide production. Endothelial dysfunction is common in cardiovascular diseases such as hypertension and diabetic microvascular complications. In addition, miR-29 is a master inhibitor of extracellular matrix gene expression, which may attenuate fibrosis but could also weaken tissue structure. The goal of this study was to develop an effective miR-29 therapeutic for multiple cardiovascular diseases using mouse models. Substantial accumulation of miR-29b and effective knockdown of Lypla1 in mouse tissues were achieved using a chitosan-packaged, chemically modified miR-29b mimic (miR-29b-CH) injected systemically at 200 μg/kg body weight. miR-29b-CH, injected once every three days, significantly attenuated angiotensin II-induced hypertension over two weeks (mean arterial pressure of 128 ± 5 vs 149 ± 5 mmHg, N = 7 Scr-CH, 8 miR-29b-CH p