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Am J Physiol Renal Physiol 285: F909-F915, 2003. First published July 1, 2003; doi:10.1152/ajprenal.00160.2003
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Angiotensin II mediates LDL-induced superoxide generation in mesangial cells

So Yeon Park, Chi Young Song, Bong Cho Kim, Hye Kyoung Hong, and Hyun Soon Lee

Department of Pathology, Seoul National University College of Medicine, Seoul 110-799, Korea

Submitted 23 April 2003 ; accepted in final form 26 June 2003

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 () generation. Quiescent HMC were exposed to 50 to 200 µg/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 (AT1) 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 AT1 receptor and angiotensinogen mRNA expression in HMC. LDL incubated with HMC increased production by up to 3.3 times compared with the level of control cells. The LDL-induced, increased generation was suppressed by losartan, DPI, or apocynin. LDL significantly increased mesangial [3H]thymidine or [3H]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 production, and cell proliferation and hypertrophy, these effects of ANG II being mediated by the AT1 receptor.

lipids; AT1 receptor; nicotinamide adenine dinucleotide phosphate oxidase; hyperplasia; hypertrophy



Address for reprint requests and other correspondence: H. S. Lee, Dept. of Pathology, Seoul National Univ. College of Medicine, Chongno-gu, Yongon-Dong 28, Seoul 110-799, Korea (E-mail: hyunsoon{at}plaza.snu.ac.kr).




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The Role of Oxidative Stress-Altered Lipoprotein Structure and Function and Microinflammation on Cardiovascular Risk in Patients with Minor Renal Dysfunction
J. Am. Soc. Nephrol., March 1, 2004; 15(3): 538 - 548.
[Abstract] [Full Text] [PDF]




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