Gap junction remodeling in hypertrophied left ventricles of aortic-banded rats: Prevention by angiotensin II type 1 receptor blockade
Gap junction remodeling in hypertrophied left ventricles of aortic-banded rats: Prevention by angiotensin II type 1 receptor blockade
复制标题
DOI：
10.1006/jmcc.2000.1293
复制
发表时间：
2001-02-01
影响因子：
5
通讯作者：
Murata, Y
中科院分区：
文献类型：
--
作者：
Emdad, L;Uzzaman, M;Murata, Y
应用免疫共聚焦和电镜技术观察了腹主动脉缩窄所致大鼠肥厚左心室（LV）压力超负荷时间隙连接结构的重构。结扎后8至12周，大鼠出现显著的LV肥大。对照组左心室肌细胞，这表明连接蛋白43（Cx43）标记主要局限于闰盘，左心室肌细胞从acrystic-banded大鼠分散点状Cx43标记在整个细胞表面。在纵向切片的LV组织中，闰盘处的Cx 43标记的比例显著降低（对照，0.87 nu-带，0.62）。肥厚心肌闰盘的正面视图显示，闰盘中心的Cx43间隙连接减少，导致间隙连接膜占据的闰盘比例显著降低（对照，0.32 nu-带，0.24）。肥厚左心室组织的电子显微镜显示，含Cx43的缝隙连接经常从其通常位置移位，形成远离椎间盘的侧对侧接触，也表现为环形轮廓。在用血管紧张素II（AII）1型受体（AT 1）拮抗剂氯沙坦（10 mg/kg/天，11周）治疗的结扎大鼠中，不仅LV肥大，而且差距连接紊乱也明显减少。这些结果表明，左室肥厚引起的压力超负荷与Cx43缝隙连接紊乱，AII可能直接或间接地发挥重要作用，缝隙连接重塑。(C)北京：科学出版社.
Remodeling of gap-junctional organization in hypertrophied left ventricle (LV) in response to pressure overload in rats induced by abdominal aorta banding was investigated by immunoconfocal and electron microscopy. Eight to 12 weeks after banding, rats developed significant LV hypertrophy. In contrast to control LV myocytes, which showed connexin43 (Cx43) labeling largely confined to the intercalated disks, LV myocytes from aortic-banded rats showed dispersion of punctate Cx43 labeling over the entire cell surface. In LV tissues sectioned longitudinally the proportion of Cx43 label at the intercalated disk decreased significantly (control, 0.87 nu aortic-banded, 0.62). En-face views of intercalated disks of hypertrophied myocardium revealed a reduction of Cx43 gap junctions in the disk center, giving rise to a significant decrease in the proportion of the disk occupied by gap-junctional membrane (control, 0.32 nu aortic-banded, 0.24). Electron microscopy of hypertrophied LV tissue revealed that Cx43-containing gap junctions were frequently displaced from their usual locations to form side-to-side contacts distant From the disk, and also appeared as annular profiles. In aortic-banded rats treated with the angiotensin II (AII) type 1 receptor (AT1) antagonist, losartan (10 mg/kg/day, 11 weeks) not only LV hypertrophy, but also the gap junction disorganization was markedly reduced. These results suggest that LV hypertrophy induced by pressure overload is associated with Cx43 gap junction disorganization and that AII may play an important role either directly or indirectly in gap-junctional remodeling. (C) 2001 Academic Press.