Deletion of LOX-1 attenuates renal injury following angiotensin II infusion

作者：Hu, Changping; Kang, Bum Yong; Megyesi, Judit; Kaushal, Gur P; Safirstein, Robert L; Mehta, Jawahar L^*

来源：Kidney International, 2009, 76(5): 521-527.

DOI：10.1038/ki.2009.234

• angiotensin
• hypertension
• LOX-1
• oxidative stress
• renal dysfunction

Angiotensin II upregulates the expression of LOX-1, a recently identified oxidized low-density lipoprotein receptor controlled by redox state which in turn upregulates angiotensin II activity on its activation. To test whether interruption of this positive feedback loop might reduce angiotensin II-induced hypertension and subsequent renal injury, we studied LOX-1 knockout mice. After infusion with angiotensin II for 4 weeks systolic blood pressure gradually increased in the wild-type mice; this rise was significantly attenuated in the LOX-1 knockout mice. Along with the rise in systolic blood pressure, renal blood urea nitrogen and creatinine) decreased in the wild-type mice, but the deterioration of function was significantly less in the LOX-1 knockout mice. Glomerulosclerosis, arteriolar sclerosis, tubulointerstitial damage, and renal collagen accumulation were all significantly less in the LOX- 1 knockout mice. The reduction in collagen formation was accompanied by a decrease in connective tissue growth factor mRNA, angiotensin type 1 receptor expression, and phosphorylation of p38 and p44/42 mitogen-activated protein kinases. Expression of endothelial nitric oxide synthase was increased in the kidneys of the LOX- 1 knockout mice compared to the wild-type mice. Overall, our study suggests that LOX-1 is a key modulator in the development of angiotensin II-induced hypertension and subsequent renal damage.

• 出版日期2009-9
• 单位中南大学