Angiotensin II type 2 receptor overexpression preserves left ventricular function after myocardial infarction

Article

关键词: CONVERTING ENZYME-INHIBITION;    CARDIAC FIBROBLASTS;    HEART-FAILURE;    GENE;    HYPERTROPHY;    AT(2);    DYSFUNCTION;    ACTIVATION;    PRESSURE;    GROWTH;   

DOI  :  10.1161/01.CIR.0000020014.14176.6D

来源: SCIE

【 摘 要 】

Background-The role of the angiotensin II type 2 receptor (AT-R) in left ventricular (LV) remodeling may depend on the underlying stimulus. We hypothesized that cardiac AT-R overexpression in transgenic (TG) mice would attenuate remodeling after myocardial infarction (MI). Methods and Results-Ten wild-type (WT) C57BL/6 mice and 12 TG mice that overexpress the AT-R in the heart were studied by cardiac MRI at baseline and days 1, 7, and 28 post-MI induced by 1 hour of Occlusion of the LAD followed by reperfusion. Short-axis imaging from apex to base was used to determine LV mass index, end-diastolic and end-systolic volume indices (EDVI, ESVI), regional wall thickness and thickening, and ejection fraction (EF). Gadolinium-DTPA was infused 20 minutes before day 1 imaging to assess infarct size. At baseline, heart rate, blood pressure, LV mass index, and EDVI were similar between groups. Baseline ESVI was lower (0.20+/-0.07 versus 0.45+/-0.15 muL/g, P<0.001) and EF higher (82.3+/-4.9% versus 67.7+/-5.3%, P<0.001) in TG than WT. Infarct size was similar (36.6+/-7.2% in WT, 34.0+/-7.8% in TG, P=NS). When controlled for baseline differences, ESVI was significantly less and EF significantly higher at all time points in TG versus WT. At day 28 ESVI was 1.05+/-0.32 muL/g in TG and 1.63+/-0.41 muL/g in WT, P<0.03. and EF was 47.3+/-5.8% versus 34.1+/-9.2%, P<0.003, respectively, Regional wall thickness and thickening were greater in TG both at baseline and at day 28. At day 28, blood pressure and. LV dP/dt were higher in TG. Conclusions-Cardiac AT-R overexpression improves LV systolic function at baseline and preserves function during post-MI remodeling.

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