Du X J, Gao X M, Wang B, Jennings G L, Woodcock E A, Dart A M
Baker Medical Research Institute and the Alfred Heart Centre, Alfred Hospital, Melbourne, Victoria, Australia.
Cardiovasc Res. 2000 Dec;48(3):448-54. doi: 10.1016/s0008-6363(00)00187-5.
To explore long-term cardiac phenotype in transgenic (TG) mice with 300-fold overexpression of beta(2)-adrenergic receptors (AR).
Echocardiography was performed serially on a cohort of wild-type and TG mice (n=26 each) between 4 and 15 months of age. Survival was monitored and autopsy and histological examinations were performed.
Heart rate was higher in TG than in wild-type mice throughout the study period. The left ventricular dimensions and fractional shortening were similar between TG and wild-type groups during 4-6 months. Starting at 9 months, however, TG mice showed progressive reduction in fractional shortening and systolic wall thickening, and increase in left ventricular dimensions and left ventricular mass, indicating onset of heart failure, left ventricular hypertrophy and remodeling. Abnormal waveforms in the electrocardiogram and episodes of ventricular ectopic beats were also observed in TG mice. Death of TG mice started at 8.5 months, and the cumulative mortality was 81% by 15 months (P<0.0001 vs. 4% in wild-type mice). The majority of deaths were due to severe heart failure, indicated by cardiac dilatation, lung congestion, pleural effusion and atrial thrombus. Left ventricular sections showed widespread interstitial fibrosis, loss of myocytes and myocyte hypertrophy in TG mice.
A high level of beta(2)AR overexpression results in cardiomyopathy and heart failure. The onset was slower and the expression levels of receptors required are much higher than previously described for the beta(1)AR overexpression.
探讨β₂ - 肾上腺素能受体（AR）过表达300倍的转基因（TG）小鼠的长期心脏表型。
对一组野生型和TG小鼠（每组n = 26）在4至15月龄期间连续进行超声心动图检查。监测生存率，并进行尸检和组织学检查。
在整个研究期间，TG小鼠的心率高于野生型小鼠。在4至6个月期间，TG组和野生型组的左心室尺寸和缩短分数相似。然而，从9个月开始，TG小鼠的缩短分数和收缩期室壁增厚逐渐降低，左心室尺寸和左心室质量增加，表明出现心力衰竭、左心室肥厚和重塑。TG小鼠还观察到心电图异常波形和室性早搏发作。TG小鼠在8.5个月开始死亡，到15个月时累积死亡率为81%（与野生型小鼠的4%相比，P < 0.0001）。大多数死亡是由于严重心力衰竭，表现为心脏扩张、肺充血、胸腔积液和心房血栓。TG小鼠的左心室切片显示广泛的间质纤维化、心肌细胞丢失和心肌细胞肥大。
高水平的β₂AR过表达导致心肌病和心力衰竭。发病较慢，所需的受体表达水平远高于先前描述的β₁AR过表达。
