title: Captopril inhibits maturation of dendritic cells and maintains their tolerogenic property in atherosclerotic rats.
abstract: Atherosclerosis (AS) is a systemic disease of the immune system featuring hyperactive dendritic cells (DCs) in atherosclerotic plaques and organs. Captopril, a representative medicine of angiotensin-converting enzyme inhibitors, has been demonstrated to be effective in treating AS. However, captopril's anti-atherosclerotic mechanism is still poorly understood. Therefore, this study was primarily performed to investigate the effects of captopril on the function of DCs in vivo. AS in rats was induced by feeding them with atherogenic diets, and it was evaluated by the levels of plasma lipids and aortic cholesterol. DCs' activity was appraised by endocytic activity, mixed lymphocyte reactions and cytokine secretion. The markers of DCs (CD103, CD80, CD86 and MHC-II) and Treg (CD4(+), CD25(+) and Foxp3(+)) were assayed by western blotting analysis and flow cytometry. Cytokine level was measured by an enzyme-linked immunosorbent assay. The results showed that captopril treatment (10, 20mg/kg/d) obviously improved dyslipidemia and reduced the levels of aortic cholesterol. Captopril significantly reduced CD103, CD80, CD86 and MHC-II protein expression while increasing that of Foxp3 in aortic tissue. Further study indicated oral administration of captopril up-regulated endocytic activity and reduced the immunostimulatory function of splenic DCs. Captopril treatment also promoted IL-10 & TGF-β production while decreasing that of IL-6 & IL-12 in splenic DCs. Finally, the results of flow cytometry indicated that captopril obviously inhibited DC maturation and promoted Treg polarization. Captopril treatment was able to inhibit DC maturation and maintain their tolerogenic property, which is closely associated with DC anti-atherosclerosis activity.
authors.affiliation: Geriatric Department of the Anhui Provincial Hospital, Hefei 230001, China.
authors.forename: Hong-Qi
authors.initials: HQ
authors.lastname: Li
authors.affiliation: Geriatric Department of the Anhui Provincial Hospital, Hefei 230001, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Geriatric Department of the Anhui Provincial Hospital, Hefei 230001, China.
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.affiliation: Geriatric Department of the Anhui Provincial Hospital, Hefei 230001, China.
authors.forename: Chang-Sen
authors.initials: CS
authors.lastname: Yin
authors.affiliation: Geriatric Department of the Anhui Provincial Hospital, Hefei 230001, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Chen
authors.affiliation: Geriatric Department of the Anhui Provincial Hospital, Hefei 230001, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Tang
authors.affiliation: Geriatric Department of the Anhui Provincial Hospital, Hefei 230001, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Rong
authors.affiliation: Geriatric Department of the Anhui Provincial Hospital, Hefei 230001, China.
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: Li
authors.affiliation: Geriatric Department of the Anhui Provincial Hospital, Hefei 230001, China. Electronic address: hlp_1963@163.com.
authors.forename: Li-Qun
authors.initials: LQ
authors.lastname: Hu
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D050197:Atherosclerosis / Q000188:drug therapy* / Q000209:etiology / Q000276:immunology; D002216:Captopril / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D002784:Cholesterol / Q000378:metabolism; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D004036:Diet, Atherogenic / Q000009:adverse effects; D004195:Disease Models, Animal; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005434:Flow Cytometry; D008055:Lipids / Q000097:blood; D008297:Male; D017207:Rats, Sprague-Dawley; D019821:Simvastatin / Q000008:administration & dosage / Q000627:therapeutic use; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000187:drug effects / Q000276:immunology
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D015703:Antigens, CD; D016207:Cytokines; D008055:Lipids; D002784:Cholesterol; D002216:Captopril; D019821:Simvastatin
keywords: Atherosclerosis; CD80; CD86; Captopril; Dendritic cells