Captopril inhibits maturation of dendritic cells and maintains their tolerogenic property in atherosclerotic rats

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, captopri...

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Bibliographic Details
Published in:International immunopharmacology 2015-09, Vol.28 (1), p.715-723
Main Authors: Li, Hong-qi, Zhang, Qi, Chen, Li, Yin, Chang-sen, Chen, Ping, Tang, Jie, Rong, Rong, Li, Ting-ting, Hu, Li-qun
Format: Article
Language:English
Subjects:
Angiotensin-Converting Enzyme Inhibitors - administration & dosage
Angiotensin-Converting Enzyme Inhibitors - pharmacology
Angiotensin-Converting Enzyme Inhibitors - therapeutic use
Animals
Antigens, CD - immunology
Aorta - drug effects
Aorta - metabolism
Atherosclerosis
Atherosclerosis - drug therapy
Atherosclerosis - etiology
Atherosclerosis - immunology
Captopril
Captopril - administration & dosage
Captopril - pharmacology
Captopril - therapeutic use
CD80
CD86
Cholesterol - metabolism
Cytokines - immunology
Dendritic cells
Dendritic Cells - cytology
Dendritic Cells - drug effects
Dendritic Cells - immunology
Diet, Atherogenic - adverse effects
Disease Models, Animal
Drug Synergism
Drug Therapy, Combination
Flow Cytometry
Lipids - blood
Male
Rats, Sprague-Dawley
Simvastatin - administration & dosage
Simvastatin - therapeutic use
T-Lymphocytes, Regulatory - cytology
T-Lymphocytes, Regulatory - drug effects
T-Lymphocytes, Regulatory - immunology
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Summary: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. [Display omitted] •Captopril was firstly found to inhibit maturation of DCs in AS rats.•Captopril was firstly found to increase Tregs polarization in AS rats.•The medicines that inhibit DC maturation may be potential drugs for AS.•The anti-atherosclerosis of Captopril is associated with its immunosuppression.
ISSN:1567-5769
1878-1705
DOI:10.1016/j.intimp.2015.05.052