Angiotensin-converting enzyme inhibition attenuates hypofibrinolysis and reduces cardiac perivascular fibrosis in genetically obese diabetic mice.

摘要: Background —Obesity and insulin resistance are associated with accelerated macrovascular microvascular coronary disease, cardiomyopathic phenomena, increased concentrations activity in blood of plasminogen activator inhibitor type 1 (PAI-1), the primary physiological fibrinolysis. Methods Results —To determine whether hypofibrinolysis tissues its potential sequelae could be attenuated pharmacologically, we studied genetically modified obese mice. By 10 weeks age, mice exhibited increases left ventricular weight glucose immunoreactive blood. PAI-1 measured spectrophotometrically was significantly elevated as well. The difference compared values lean controls widened by 20 age. Perivascular fibrosis arterioles small arteries evident paralleling tissue factor expression immunohistochemical image analysis, situ hybridization, reverse transcription–polymerase chain reaction. Inhibition ACE initiated age continued for arrested increase cardiac mRNA well perivascular fibrosis. Conclusions —Thus, inhibition proteo(fibrino)lysis augmented heart precede may contribute to seen obesity resistance. Furthermore, can attenuate all 3 phenomena.