title: Curcumin Exerts its Anti-hypertensive Effect by Down-regulating the AT1 Receptor in Vascular Smooth Muscle Cells.
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.
authors.affiliation: Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, P. R. China.|Chongqing Institute of Cardiology, Chongqing, P. R. China.
authors.forename: Yonggang
authors.initials: Y
authors.lastname: Yao
authors.affiliation: Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, P. R. China.|Chongqing Institute of Cardiology, Chongqing, P. R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, P. R. China.|Chongqing Institute of Cardiology, Chongqing, P. R. China.
authors.forename: Meixiang
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, P. R. China.|Chongqing Institute of Cardiology, Chongqing, P. R. China.
authors.forename: Hongmei
authors.initials: H
authors.lastname: Ren
authors.affiliation: Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, P. R. China.|Chongqing Institute of Cardiology, Chongqing, P. R. China.
authors.forename: Caiyu
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, P. R. China.|Chongqing Institute of Cardiology, Chongqing, P. R. China.
authors.forename: Jialiang
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, P. R. China.|Chongqing Institute of Cardiology, Chongqing, P. R. China.
authors.forename: Wei Eric
authors.initials: WE
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, P. R. China.|Chongqing Institute of Cardiology, Chongqing, P. R. China.|Department of Nutrition, Daping Hospital, The Third Military Medical University, Chongqing, P. R. China.
authors.forename: Jian
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, P. R. China.|Chongqing Institute of Cardiology, Chongqing, P. R. China.
authors.forename: Chunyu
authors.initials: C
authors.lastname: Zeng
mesh_terms: D000804:Angiotensin II; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D002460:Cell Line; D003474:Curcumin / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control; D008638:Mesenteric Arteries / Q000187:drug effects / Q000502:physiology; D008810:Mice, Inbred C57BL; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics / Q000378:metabolism*; D016329:Sp1 Transcription Factor / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: D000959:Antihypertensive Agents; D044140:Receptor, Angiotensin, Type 1; D016329:Sp1 Transcription Factor; D000804:Angiotensin II; D003474:Curcumin