TY - JOUR
T1 - Losartan inhibits proliferation and inflammation of vascular smooth muscle cells by modulation of uric acid transporter
AU - Kang, Seok Min
AU - Chang, Woochul
AU - Lim, Soyeon
AU - Song, Byeong Wook
AU - Kim, Hye Jung
AU - Cha, Min Ji
AU - Oh, Jaewon
AU - Jang, Yangsoo
AU - Chung, Namsik
AU - Hwang, Ki Chul
PY - 2008/9/1
Y1 - 2008/9/1
N2 - 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.
AB - 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.
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M3 - Article
AN - SCOPUS:80051963865
VL - 5
SP - 521
EP - 527
JO - Tissue Engineering and Regenerative Medicine
JF - Tissue Engineering and Regenerative Medicine
SN - 1738-2696
IS - 3
ER -