Angiotensin II-Induced Cardiac Remodeling

Wild-type mice and PAI-1^−/− mice were infused with AngII (1 μg/kg/min; Sigma-Aldrich) or a vehicle control (PBS) using an osmotic minipump (Alzet, model 1002) as previously described^{18 (link)}; 9 to 10 male and female mice (16–20 weeks old) were used per group. Pumps remained implanted for 7 or 14 days. An additional group of 6 PAI-1^−/− mice were infused with AngII as described earlier but also received injections of 300 μg/kg recombinant human BMP-7 in PBS (R&D Systems) every other day starting the day of minipump implantation. Arterial pressures were measured using the Coda2 noninvasive cuff system (Kent Scientific) for ≥8 consecutive measurements. Heart and tibia were extracted at day 7 or 28 after initiation of AngII. Transthoracic 2-dimensional M-mode echocardiography was performed using the Vevo770 (VisualSonics) equipped with a 30-MHz transducer. Mice were lightly anesthetized using a mixture of 1.5% isofluorane and oxygen (2 L/min) to ensure heart rates >400 to 450 bpm. Change in left ventricular area during the cardiac cycle was determined by endocardial border tracings to determine ejection fraction (average of parasternal long and short axis measurements). M-mode tracings were used to measure left ventricular systolic and diastolic chamber dimensions. The mean value from 3 beats was determined for each parameter.