Role of Activated Renin-Angiotensin System in Myocardial Fibrosis and Left Ventricular Diastolic Dysfunction in Diabetic Patients Reversal by Chronic Angiotensin II Type 1A Receptor Blockade

Abstract

We attempted to test the hypothesis that chronic angiotensin II type 1A receptor blockade (ARB) alters myocardial collagen turnover leading to an improvement of diastolic dysfunction in diabetic patients. Forty-eight type 2 diabetic patients were divided into 2 groups: 38 treated with candesartan for 6 months, and 10 without candesartan, as controls. Doppler mitral flow velocity pattern and biomarkers of collagen type I turnover were assessed before and after ARB during a 6-month period. The mitral E/A ratio increased from 0.65+/-0.11 to 0.75+/-0.19. The carboxy-terminal propeptide of procollagen type I (PIP), an index of collagen type I synthesis, decreased and the carboxy-terminal telopeptide of collagen type I (CITP), an index of collagen type I degradation, increased following ARB. Consequently, the PIP/CITP ratio, an index of coupling between the synthesis and degradation of collagen type I, decreased. None of the indexes changed in the control group. The change in left ventricular chamber stiffness did not correlate with the change in PICP (r=0.08, p=NS), but it did with the changes in CITP or in the PIP/CITP ratio (r=0.35, p<0.05; r=0.39, p<0.05). Chronic ARB improves diastolic dysfunction in diabetic patients, at least partially through the attenuation of myocardial fibrosis, by regulating collagen turnover, particularly by facilitating collagen degradation.