Grant: Operating Grant

Hypertension is a medical condition in which the blood pressure is chronically elevated. Persistent hypertension is one of the risk factors for vascular diseases, strokes, heart attacks, heart and kidney failure. Hypertension is invariably associated with the development of diabetic nephropathy (DN). Blood pressure is regulated by a hormonal system, called renin-angiotensin system (RAS). Indeed, clinical and experimental studies demonstrate that chronic administration with inhibitors of angiotensin-converting enzyme (ACE) or angiotensin II receptor blockers (ARBs) are effective in reducing the blood pressure and ameliorating nephropathy progression as well as reducing morbidity and mortality in hypertensives and diabetic patients but not the cure. These studies demonstrate that RAS activation is a major risk factor in the pathogenesis of hypertension and nephropathy in diabetes. Angiotensinogen is the sole substrate in the RAS and it is highly expressed in the kidney. This proposal, which concerns the molecular mechanism(s) of regulation of angiotensinogen gene expression by a novel molecule, called heterogenous nuclear ribonucleoprotein F in diabetic kidneys, will increase our knowledge and understanding the regulation of intrarenal RAS activation in diabetes and its role(s) in the pathogenesis of hypertension and nephropathy, thereby contributing directly to improved clinical treatment of hypertension development and nephropathy progression in diabetes.