Hyperuricemia has known to be a risk factor for coronary artery disease, hypertension, and heart failure. Among angiotensin II receptor blockers(ARBs), only losartan lowers serum uric acid(UA) level compared with other ARBs. Recent studies have reported that UAcauses vascular smooth muscle cells(VSMCs) proliferation and inflammation by entering cells via a functional uric acid transporter(UAT). We investigated whether losartan could inhibit the UA-stimulated proliferative and inflammatory signaling activation by modulation of UAT in cultured rat aortic VSMCs. Following 72 hours incubation of UA, proliferation of VSMCs was increased dose-dependently. Losartan inhibited UA-stimulatedproliferation in dose-dependent manner with an IC50 value of about 1 M. Losartan attenuatedp38, ERKs activation, COX-2 expression, and MCP-1 production. Losartan significantly decreased expression of UAT in UA-stimulated VSMCs(33% reduction, p<0.05), which suggests inhibitory effect of losartan on the uptake of UA via UAT. These data provide that losartan may involve anti-inflammatory and antiproliferative activity by modulating UAT. Therefore, losartan may provide beneficial effect on vascular changes in hyperuricemic condition.
|Number of pages||7|
|Journal||Tissue Engineering and Regenerative Medicine|
|Publication status||Published - 2008 Sept|
Bibliographical noteFunding Information:
This research was supported by grants from the National Institutes of Health (DK-31135) and the Faculty Research Award Program of the City University of New York. The author thanks Dr Karen Ackroff for her helpful comments. Address reprint requests to: Anthony Selafani, Department of Psychology, Brooklyn College of CUNY, Brooklyn, NY 11210, U.S.A.
All Science Journal Classification (ASJC) codes
- Medicine (miscellaneous)
- Biomedical Engineering