Abstract
Curcumin exerts beneficial effects on cardiovascular diseases, including hypertension. However, its mechanisms are unknown. We propose that curcumin prevents the development of hypertension by regulating AT1 receptor (AT1R) expression in arteries. The present study examined how curcumin regulates AT1R expression in vascular smooth muscle cells and investigated the physiological significance of this regulation in angiotensin (Ang) II-induced hypertension. The results showed that curcumin decreased AT1R expression in a concentration- and time-dependent manner in vascular smooth muscle cells. Using luciferase reporters with an entire AT1 or a mutant AT1R in A10 cells, the AT1R promoter activity was inhibited by 10−6 M curcumin, and the proximal element (from −61 to +25 bp) of the AT1R promoter was crucial for curcumin-induced AT1R down-regulation. An electrophoretic mobility shift assay showed that curcumin decreased specificity protein 1 (SP1) binding with the AT1R promoter in A10 cells. Curcumin treatment reduced Ang II-induced hypertension in C57Bl/6J mice, which was accompanied by lower AT1R expression in the arteries and decreased Ang II-mediated vasoconstriction in the mesenteric artery. These findings indicate that curcumin down-regulates AT1R expression in A10 cells by affecting SP1/AT1R DNA binding, thus reducing AT1R-mediated vasoconstriction and subsequently prevents the development of hypertension in an Ang II-induced hypertensive model.
Highlights
Curcumin exerts beneficial effects on cardiovascular diseases, including hypertension
These findings indicate that curcumin down-regulates Angiotensin II (Ang II) type-1 receptor (AT1R) expression in A10 cells by affecting specificity protein 1 (SP1)/AT1R DNA binding, reducing AT1Rmediated vasoconstriction and subsequently prevents the development of hypertension in an Ang
Western blot analysis revealed that curcumin decreased AT1R protein levels significantly at 10−8 mol/L compared with the control level, and the reduction reached a maximum at 10−5 mol/L (Fig. 1A)
Summary
Curcumin exerts beneficial effects on cardiovascular diseases, including hypertension. Curcumin treatment reduced Ang II-induced hypertension in C57Bl/6J mice, which was accompanied by lower AT1R expression in the arteries and decreased Ang II-mediated vasoconstriction in the mesenteric artery These findings indicate that curcumin down-regulates AT1R expression in A10 cells by affecting SP1/AT1R DNA binding, reducing AT1Rmediated vasoconstriction and subsequently prevents the development of hypertension in an Ang. The renin-angiotensin system (RAS) is one of the most important regulators of arterial blood pressure, and RAS activation is related to the pathogenesis of hypertension[1]. The results shows that, via affecting specificity protein 1 (SP1)/AT1R DNA binding, curcumin down-regulated AT1R expression in A10 cells, reduced AT1R-mediated vasoconstriction, and subsequently prevented the development of hypertension in an Ang II-induced hypertensive model
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