Wang Z-C, Qi J, Liu L-M, Li J, Xu H-Y, Liang B, Li B
Shanxi Medical University, Taiyuan, Shanxi, China.
Eur Rev Med Pharmacol Sci. 2017 Mar;21(5):1159-1168.
Valsartan has been reported to have the function of treating hypertension and improving the prognosis of patients. Many studies indicated that valsartan can also increase angiotensin II, andosterone and plasma renin activity (PRA). Autoantibodies against the angiotensin II type 1 receptor (AT1-AA) have been showed to increase reactive oxygen species (ROS) and calcium (Ca2+) and result in apoptosis in vascular smooth muscle cells. In this study, we attempted to explore the effect of valsartan on AT1-AA-induced apoptosis in endothelial progenitor cells.
Endothelial progenitor cells (EPCs) were cultured. The cytotoxicity was determined by MTT assay. EPCs apoptosis was determined by DAPI staining and flow cytometry. Reactive oxygen species, intracellular calcium concentration and calpain activity were measured using Fluostar Omega Spectrofluorimeter. The expression of p-ERK, p-eIF-2a, CHOP, Bcl-2 and caspase-3 were detected by Western blot.
MTT assays showed valsartan significantly inhibited AT1-AA- induced decline of the viability of EPCs. DAPI staining and flow cytometry results indicated valsartan inhibited AT1-AA-induced decline of the viability of EPCs via inhibiting AT1-AA-induced apoptosis. Furthermore, the increasing of reactive oxygen species, intracellular calcium and calpain activity induced by AT1-AA in EPCs were also recovered after pre-treated with valsartan. Meanwhile, the upregulation of p-ERK, p-eIF-2a and CHOP, downregulation of Bcl-2, and activation of Caspase-3 caused by AT1-AA were reversed after pre-incubated with valsartan.
Valsartan could inhibit AT1-AA-induced apoptosis through inhibiting oxidative stress mediated ER stress in EPCs.
据报道缬沙坦具有治疗高血压和改善患者预后的作用。许多研究表明，缬沙坦还可增加血管紧张素 II、醛固酮和血浆肾素活性（PRA）。针对血管紧张素 II 1 型受体的自身抗体（AT1 - AA）已被证明可增加活性氧（ROS）和钙（Ca2+），并导致血管平滑肌细胞凋亡。在本研究中，我们试图探讨缬沙坦对 AT1 - AA 诱导的内皮祖细胞凋亡的影响。
培养内皮祖细胞（EPCs）。通过 MTT 法测定细胞毒性。通过 DAPI 染色和流式细胞术测定 EPCs 凋亡。使用 Fluostar Omega 荧光分光光度计测量活性氧、细胞内钙浓度和钙蛋白酶活性。通过蛋白质免疫印迹法检测 p - ERK、p - eIF - 2a、CHOP、Bcl - 2 和半胱天冬酶 - 3 的表达。
MTT 试验表明缬沙坦显著抑制 AT1 - AA 诱导的 EPCs 活力下降。DAPI 染色和流式细胞术结果表明缬沙坦通过抑制 AT1 - AA 诱导的凋亡来抑制 EPCs 活力下降。此外，用缬沙坦预处理后，EPCs 中由 AT1 - AA 诱导的活性氧、细胞内钙和钙蛋白酶活性的增加也得到恢复。同时，用缬沙坦预孵育后，由 AT1 - AA 引起的 p - ERK、p - eIF - 2a 和 CHOP 的上调、Bcl - 2 的下调以及半胱天冬酶 - 3 的激活均被逆转。
缬沙坦可通过抑制 EPCs 中氧化应激介导的内质网应激来抑制 AT1 - AA 诱导的凋亡。
