Yamada T, Akishita M, Pollman M J, Gibbons G H, Dzau V J, Horiuchi M
Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Life Sci. 1998;63(19):PL289-95. doi: 10.1016/s0024-3205(98)00448-2.
Angiotensin II type 2 (AT2) receptor is expressed abundantly in the fetal vasculature with rapid decline after birth and re-expressed in the adult vasculature after injury, whereas angiotensin II type 1 (AT1) receptor is expressed. We studied their effects on apoptosis in cultured rat vascular smooth muscle cells (VSMC). Serum starvation induced VSMC DNA fragmentation and the stimulation of AT1 receptor inhibited this apoptotic change. We transfected rat AT2 receptor cDNA, since cultured adult VSMCs show very low level of endogenous AT2 receptor. In AT2 receptor transfected VSMC, selective stimulation of AT2 receptor facilitated serum-deprivation-induced apoptosis and AT1 receptor stimulation inhibited it. Moreover we observed that AT1 receptor stimulation activated extracellular signal-regulated kinase (ERK), whereas the AT2 receptor stimulation inhibited the activation of ERK. Taken together, our results suggest that AT1 and AT2 receptors exert counteracting effects on ERK activation and consequently VSMC apoptosis and differential expression of these receptors may participate in vascular development and vascular remodeling.
血管紧张素II 2型（AT2）受体在胎儿血管系统中大量表达，出生后迅速下降，并在成年血管系统损伤后重新表达，而血管紧张素II 1型（AT1）受体则有表达。我们研究了它们对培养的大鼠血管平滑肌细胞（VSMC）凋亡的影响。血清饥饿诱导VSMC DNA片段化，而AT1受体的刺激抑制了这种凋亡变化。由于培养的成年VSMC显示出非常低水平的内源性AT2受体，我们转染了大鼠AT2受体cDNA。在转染了AT2受体的VSMC中，AT2受体的选择性刺激促进了血清剥夺诱导的凋亡，而AT1受体的刺激则抑制了它。此外，我们观察到AT1受体的刺激激活了细胞外信号调节激酶（ERK），而AT2受体的刺激则抑制了ERK的激活。综上所述，我们的结果表明，AT1和AT2受体对ERK激活发挥相反作用，因此对VSMC凋亡也有相反作用，并且这些受体的差异表达可能参与血管发育和血管重塑。
