Yamazaki T, Komuro I, Shiojima I, Yazaki Y
Department of Cardiovascular Medicine, Faculty of Medicine, University of Tokyo, Japan.
Ann N Y Acad Sci. 1999 Jun 30;874:38-48. doi: 10.1111/j.1749-6632.1999.tb09223.x.
Mechanical stretch induced by high blood pressure is an initial factor leading to cardiac hypertrophy. In an in vivo study, an angiotensin II (AngII) type 1 receptor antagonist TCV116 reduced left ventricular (LV) weight, LV wall thickness, transverse myocyte diameter, relative amount of V3 myosin heavy chain, and interstitial fibrosis, while treatment with hydralazine did not. In an in vitro study using cultured cardiomyocytes, mechanical stretch activated second messengers such as mitogen-activated protein (MAP) kinase, followed by increased protein synthesis. Additionally, in the stretch-conditioned medium AngII and endothelin-1 concentrations were increased. Furthermore, the Na+/H+ exchanger activated by mechanical stretch modulated the hypertrophic responses of cardiomyocytes. The pathways leading to MAP kinase activation differed between cell types. In cardiac fibroblasts AngII activated MAP kinase via G beta gamma subunit of Gi, Src, Shc, Grb2, and Ras, whereas Gq and protein kinase C were critical in cardiomyocytes.
高血压引起的机械牵张是导致心脏肥大的初始因素。在一项体内研究中，血管紧张素II（AngII）1型受体拮抗剂TCV116可降低左心室（LV）重量、LV壁厚度、横向肌细胞直径、V3肌球蛋白重链的相对含量以及间质纤维化，而肼屈嗪治疗则无此效果。在一项使用培养心肌细胞的体外研究中，机械牵张激活了丝裂原活化蛋白（MAP）激酶等第二信使，随后蛋白质合成增加。此外，在牵张条件培养基中，AngII和内皮素-1浓度升高。此外，机械牵张激活的Na+/H+交换器调节了心肌细胞的肥大反应。导致MAP激酶激活的途径在不同细胞类型之间有所不同。在心脏成纤维细胞中，AngII通过Gi的Gβγ亚基、Src、Shc、Grb2和Ras激活MAP激酶，而在心肌细胞中，Gq和蛋白激酶C起关键作用。
