Angiotensin II mediates LDL-induced superoxide generation in mesangial cells
Angiotensin II mediates LDL-induced superoxide generation in mesangial cells
复制标题
DOI：
10.1152/ajprenal.00160.2003
复制
发表时间：
2003-11-01
影响因子：
4.2
通讯作者：
Lee, HS
中科院分区：
文献类型：
--
作者：
Park, SY;Song, CY;Lee, HS
脂质异常和局部肾素-血管紧张素系统（RAS）的激活可能参与慢性肾小球疾病的发病机制。本研究探讨了低密度脂蛋白（LDL）是否激活培养的人肾小球系膜细胞（HMC）中的局部RAS，同时，ANG II是否介导LDL诱导的系膜细胞增殖、肥大和超氧化物（O-2（-））生成。将静止期HMC暴露于50 - 200 μ g/ml LDL或10（-7）-10（-10）M ANG II中0.5 - 24小时，同时加入或不加入10（-6）M氯沙坦（一种ANG II I型（AT（1））受体拮抗剂）或10（-5）M二苯甲异碘铵（DPI）或10（-4）M夹竹桃苷（烟酰胺腺嘌呤二核苷酸磷酸氧化酶的抑制剂）。LDL诱导的HMC培养基中的ANG II水平增加了三倍。LDL可上调HMC AT（1）受体和血管紧张素原mRNA的表达。与对照细胞相比，与HMC孵育的LDL使O-2（-）产生增加高达3.3倍。氯沙坦、DPI或夹竹桃麻素可抑制LDL诱导的O-2（-）生成增加。低密度脂蛋白显着增加系膜[H-3]胸苷或[H-3]亮氨酸掺入，而这些过程被废除氯沙坦。总之，LDL增加肾小球系膜细胞产生ANG II，进而导致O-2（-）产生增加，细胞增殖和肥大，ANG II的这些作用由AT（1）受体介导。
Lipid abnormalities and activation of the local renin-angiotensin system (RAS) may be involved in the pathogenesis of chronic glomerular disease. This study investigated whether low-density lipoprotein (LDL) activates local RAS in cultured human mesangial cells (HMC) and, at the same time, whether ANG II mediates LDL-induced mesangial cell proliferation, hypertrophy, and superoxide (O-2(-)) generation. Quiescent HMC were exposed to 50 to 200 mug/ml of LDL or 10(-7) to 10(-10) M ANG II for 0.5 to 24 h in the presence or absence of 10(-6) M losartan, an ANG II type I (AT(1)) receptor antagonist, or 10(-5) M diphehylendieodonium (DPI) or 10(-4) M apocynin, inhibitors of nicotinamide adenine dinucleotide phosphate oxidase. LDL induced an up to threefold increase in the ANG II levels in the culture medium of HMC. LDL upregulated AT(1) receptor and angiotensinogen mRNA expression in HMC. LDL incubated with HMC increased O-2(-) production by up to 3.3 times compared with the level of control cells. The LDL-induced, increased O-2(-) generation was suppressed by losartan, DPI, or apocynin. LDL significantly increased mesangial [H-3] thymidine or [H-3] leucine incorporation, whereas these processes were abrogated by losartan. In conclusion, LDL increases ANG II production by mesangial cells, which in turn results in increased O-2(-) production, and cell proliferation and hypertrophy, these effects of ANG II being mediated by the AT(1) receptor.