Krishnamurthy P, Subramanian V, Singh M, Singh K
Department of Physiology, James H Quillen College of Medicine, James H Quillen Veterans Affairs Medical Center, East Tennessee State University, Johnson City, Tennessee 37614, USA.
Heart. 2006 Sep;92(9):1309-15. doi: 10.1136/hrt.2005.071001. Epub 2006 Mar 17.
To study the role of beta1 integrins in left ventricular (LV) remodelling after myocardial infarction (MI).
LV structural and functional alterations were determined in wild-type (WT) and beta1 integrin heterozygous knockout (hKO) mice one month after MI. MI increased beta1 integrin expression in both groups; however, the increase was lower in hKO. Infarct size was similar in WT and hKO mice, whereas lung wet weight to dry weight ratio was increased in the hKO-MI mice (5.17 (SE 0.13) v 4.60 (0.15) in WT-MI, p < 0.01). LV end systolic and end diastolic diameters were significantly higher and percentage fractional shortening was significantly lower in hKO-MI. The ratio of peak velocity of early LV filling (E wave) to that of the late LV filling (A wave) and the isovolumic relaxation time (IVRT) were increased in both MI groups but the increase in IVRT was significantly higher in hKO-MI group than in WT-MI mice. Langendorff perfusion analysis indicated reduced peak LV developed pressure and increased LV end diastolic pressure in both MI groups. The reduction in peak LV developed pressure (36.7 (2.2) v 53.4 (1.9) mm Hg, p < 0.05) and increase in LV end diastolic pressure was higher in hKO-MI than in WT-MI. Increase in fibrosis was not different between the two MI groups. The increase in myocyte circumference was higher in the hKO-MI group (p < 0.001 v WT-MI). The number of apoptotic myocytes was significantly higher in hKO-MI than in WT-MI mice (p < 0.005) three days after MI. The number of necrotic myocytes was not different between the two MI groups.
beta1 integrins are crucial in post-MI remodelling with effects on LV function, hypertrophy and apoptosis.
研究β1整合素在心肌梗死（MI）后左心室（LV）重构中的作用。
在MI后1个月，测定野生型（WT）和β1整合素杂合敲除（hKO）小鼠的LV结构和功能改变。MI使两组中的β1整合素表达均增加；然而，hKO组的增加幅度较小。WT和hKO小鼠的梗死面积相似，而hKO-MI小鼠的肺湿重与干重之比增加（WT-MI组为4.60（0.15），hKO-MI组为5.17（标准误0.13），p<0.01）。hKO-MI组的LV收缩末期和舒张末期直径显著更高，而射血分数百分比显著更低。两个MI组的LV早期充盈峰值速度（E波）与晚期充盈峰值速度（A波）之比以及等容舒张时间（IVRT）均增加，但hKO-MI组IVRT的增加显著高于WT-MI小鼠。Langendorff灌注分析表明，两个MI组的LV峰值发展压力降低，LV舒张末期压力增加。hKO-MI组LV峰值发展压力的降低幅度（36.7（2.2）对53.4（1.9）mmHg，p<0.05）和LV舒张末期压力的增加幅度高于WT-MI组。两组MI之间的纤维化增加没有差异。hKO-MI组的心肌细胞周长增加幅度更高（与WT-MI组相比，p<0.001）。MI后3天，hKO-MI组的凋亡心肌细胞数量显著高于WT-MI小鼠（p<0.005）。两组MI之间坏死心肌细胞的数量没有差异。
β1整合素在MI后重构中至关重要，对LV功能、肥大和凋亡有影响。
