Uric acid stimulates vascular smooth muscle cell proliferation and oxidative stress via the vascular renin-angiotensin system
Uric acid stimulates vascular smooth muscle cell proliferation and oxidative stress via the vascular renin-angiotensin system
复制标题
DOI：
10.1097/hjh.0b013e3282f240bf
复制
发表时间：
2008-02-01
影响因子：
4.9
通讯作者：
Tuck, Michael L.
中科院分区：
文献类型：
--
作者：
Corry, Dalila B.;Eslami, Pirooz;Tuck, Michael L.
背景：血浆尿酸与多种疾病的高血压有关，并已被证明是高血压的预测指标。尿酸在高血压发生发展中的作用机制尚不清楚。方法我们验证了尿酸通过刺激血管肾素血管紧张素系统（RAS）刺激血管平滑肌细胞（VSMC）增殖和氧化应激的假说。将大鼠VSMC暴露于0-300 μ mol尿酸中48 h。结果尿酸（200 μ mol和300 μ mol）刺激VSMC增殖。10（-6）mol氯沙坦或10（-6）mol卡托普利可抑制这种作用。尿酸孵育VSMC 48小时也增加血管紧张素原信使RNA表达和细胞内血管紧张素II浓度。这些反应也被氯沙坦和卡托普利抑制。血管紧张素原mRNA的表达增加也被抑制与PD 98059，一种丝裂原活化蛋白（MAP）激酶抑制剂共孵育。尿酸刺激VSMC产生过氧化氢和8-异前列腺素。这些增加的氧化应激指标显着减少共同孵育的细胞与卡托普利或氯沙坦。尿酸也降低了亚硝酸盐和硝酸盐的浓度在培养基中，一种效果，防止氯沙坦和captopripl.Conclusion这些结果表明，尿酸刺激增殖，血管紧张素II的生产，并通过组织RAS氧化应激在VSMC。这表明尿酸通过刺激血管RAS引起心血管疾病，并且这种刺激可能由MAP激酶途径介导。
Background Plasma uric acid has been associated with hypertension in a variety of disorders, and has been shown to be predictive of hypertension. The mechanistic role of uric acid in the development of hypertension is not known however.Method We tested the hypothesis that uric acid stimulates vascular smooth muscle cell (VSMC) proliferation and oxidative stress by stimulating the vascular renin angiotensin system (RAS). Rat VSMC were exposed to 0-300 mu mol uric acid for 48 h.Results Uric acid (200 and 300 mu mol) stimulated the proliferation of VSMC as measured by thymidine uptake. This effect was prevented by 10(-6) mol losartan or by 10(-6) mol captopril. Incubation of VSMC with uric acid for 48 h also increased angiotensinogen messenger RNA expression and intracellular concentrations of angiotensin II. These responses were also inhibited by losartan and captopril. Increased expression of angiotensinogen mRNA was also inhibited by co-incubation with PD 98059, a mitogen-activated protein (MAP) kinase inhibitor. Uric acid stimulated the production of hydrogen peroxide and 8-isoprostane in VSMC. These increases in oxidative stress indicators were significantly reduced by co-incubating the cells with captopril or losartan. Uric acid also decreased nitrite and nitrate concentrations in the culture medium, an effect that was prevented by losartan and captopril.Conclusion These results demonstrate that uric acid stimulates proliferation, angiotensin II production, and oxidative stress in VSMC through tissue RAS. This suggests that uric acid causes cardiovascular disorders by stimulating the vascular RAS, and this stimulation may be mediated by the MAP kinase pathway.