Effects of angiotensin II and insulin on ERK1/2 activation in fibroblasts from hypertensive patients
Effects of angiotensin II and insulin on ERK1/2 activation in fibroblasts from hypertensive patients
复制标题
DOI：
10.1016/j.amjhyper.2004.02.017
复制
发表时间：
2004-07-01
影响因子：
3.2
通讯作者：
Semplicini, A
中科院分区：
文献类型：
--
作者：
Sartori, M;Ceolotto, G;Semplicini, A
背景：胰岛素抵抗是高血压患者常见的现象，可加速心血管损害。血管紧张素11和胰岛素信号通路之间的相互作用可能引起胰岛素抵抗，并可能导致心血管损伤的发展。为了确定代谢紊乱和心血管重塑之间的共同病理生理途径，我们研究了血管紧张素II和胰岛素对细胞外信号调节激酶I和2（ERK 1/2）的影响，ERK 1/2是参与细胞增殖和细胞外基质沉积的丝裂原活化蛋白激酶（MAPK）的亚型。培养来自正常血压受试者、胰岛素敏感性高血压受试者和胰岛素抵抗性高血压受试者的皮肤成纤维细胞，并在四次传代后使用。分别使用抗ERK 1/2和抗pERK 1/2的特异性抗体通过Western印迹测量ERK 1/2表达和磷酸化。AT，血管紧张素11受体的表达测定通过逆转录-聚合酶链反应在真实的time.Results：ERK 1/2相似地表达在皮肤成纤维细胞从所有组; ERK 1/2磷酸化引起的血管紧张素11是显着较高的成纤维细胞从高血压患者相比，血压正常的科目，但增加只观察到在胰岛素抵抗性高血压科目。胰岛素对ERK 1/2磷酸化的影响在三组中没有显著差异。在正常血压受试者和胰岛素敏感性高血压受试者中，与单一激动剂相比，胰岛素和血管紧张素11联合治疗可在更大程度上增加ERK 1/2磷酸化，但在胰岛素抵抗性高血压受试者中则不然。胰岛素抵抗性高血压患者血管紧张素11刺激的ERK 1/2活化增加，它可能在胰岛素抵抗和加速心血管损伤的发病机制中起作用。(C)2004年美国高血压杂志有限公司
Background: Insulin resistance, a frequent finding in hypertensive patients, leads to accelerated cardiovascular damage. It has been suggested that a crosstalk between angiotensin 11 and insulin signaling pathways may provoke insulin resistance, and may contribute to the development of cardiovascular damage. To identify a common pathophysiologic pathway between metabolic disorders and cardiovascular remodeling, we investigated the effect of angiotensin II and insulin on extracellular signal regulated kinases I and 2 (ERK1/2), isoforms of mitogen-activated protein kinases (MAPK) involved in cellular proliferation and extracellular matrix deposition.Methods: Skin fibroblasts from normotensive subjects' insulin sensitive hypertensive subjects, and insulin resistant hypertensive subjects were cultured and used after four passages. The ERK1/2 expression and phosphorylation were measured by Western blot using specific antibodies, respectively anti-ERK1/2 and anti-pERK1/2. Expression of AT, receptor for angiotensin 11 was determined by reverse transcriptase-polymerase chain reaction in real time.Results: The ERK1/2 were similarly expressed in skin fibroblasts from all groups; ERK1/2 phosporylation evoked by angiotensin 11 was significantly higher in fibroblasts from hypertensive patients in comparison to normotensive subjects, but the increase was observed only in insulin resistant hypertensive subjects. The effect of insulin on ERK1/2 phosphorylation was not significantly different in the three groups. Treatment with the combination of insulin and angiotensin 11 increased ERK1/2 phosphorylation to a greater extent in comparison to the single agonists in normotensive subjects and in insulin sensitive but not in insulin resistant hypertensive subjects.Conclusions: Angiotensin 11 stimulated ERK1/2 activation is increased in insulin resistant hypertensive subjects, and it may play a role in the pathogenesis of insulin resistance and accelerated cardiovascular damage. (C) 2004 American Journal of Hypertension, Ltd.