Department of Endocrinology and Metabolism, Southwest Hospital, Third Military Medical University, No. 30, Gaotanyanzheng Street, Shapingba District, Chongqing, 400038, China.
Endocrine. 2015 Feb;48(1):135-42. doi: 10.1007/s12020-014-0239-5. Epub 2014 Mar 28.
Hyperuricemia is recently reported involving in various obesity-related cardiovascular disorders, especially hypertension. However, the underlying mechanisms are not completely understood. In the present study, we investigated whether uric acid upregulates renin-angiotensin system (RAS) expression in adipocytes. We also examined whether RAS activation plays a role in uric acid-induced oxidative stress in adipocytes. The adipocytes of different phenotypes were incubated with uric acid for 48 h, respectively. Losartan (10(-4) M) or captopril (10(-4) M) was used to block adipose tissue RAS activation. mRNA expressions of angiotensinogen (AGT), angiotensin-converting enzyme-1 (ACE-1), renin, angiotensin type 1 receptor (AT1R), and angiotensin type 2 receptor (AT2R) were evaluated with real-time PCR. Angiotensin II concentrations in supernatant were measured by ELISA. Intracellular reactive species (ROS) levels were measured by fluorescent probe DCFH-DA, DHR, or NBT assay. The uric acid upregulated both RAS (AGT, ACE1, renin, AT1R, and AT2R) mRNA expressions and angiotensin II protein secretion and caused a significant increase in ROS production in 3T3-L1 adipocytes. These effects could be prevented by RAS inhibitors, either losartan or captopril. RAS activation has been causally implicated in oxidative stress induced by uric acid in 3T3-L1 adipocytes, suggesting a plausible mechanism through which hyperuricemia contributes to the pathogenesis of obesity-related cardiovascular diseases.
高尿酸血症最近被报道与各种肥胖相关的心血管疾病有关，尤其是高血压。然而，其潜在机制尚不完全清楚。在本研究中，我们研究了尿酸是否会在上皮细胞中上调肾素-血管紧张素系统 (RAS) 的表达。我们还研究了 RAS 激活是否在尿酸诱导的上皮细胞氧化应激中起作用。分别用尿酸孵育不同表型的脂肪细胞 48 小时。用氯沙坦（10(-4) M）或卡托普利（10(-4) M）阻断脂肪组织 RAS 激活。用实时 PCR 评估血管紧张素原 (AGT)、血管紧张素转换酶 1 (ACE-1)、肾素、血管紧张素 1 型受体 (AT1R) 和血管紧张素 2 型受体 (AT2R) 的 mRNA 表达。通过 ELISA 测量上清液中的血管紧张素 II 浓度。通过荧光探针 DCFH-DA、DHR 或 NBT 测定法测量细胞内活性物质 (ROS) 水平。尿酸可上调 RAS（AGT、ACE1、肾素、AT1R 和 AT2R）mRNA 表达和血管紧张素 II 蛋白分泌，并导致 3T3-L1 脂肪细胞中 ROS 产生显著增加。RAS 抑制剂氯沙坦或卡托普利可预防这些作用。RAS 激活已被证明与尿酸诱导的 3T3-L1 脂肪细胞氧化应激有关，这表明高尿酸血症导致肥胖相关心血管疾病发病机制的一种可能机制。
