Cyclodextrin Ameliorates The Progression Of Atherosclerosis Via Increasing HDL-C Plasma Levels And Anti-inflammatory Effects In Rabbits

Atherosclerotic cardiovascular disease is a major cause of morbidity and mortality worldwide.Increased circulating cholesterol levels and inflammation in the arterial wall characterize atherosclerosis.The atheosclerotic plaque is characterizedby the accumulation of lipids,inflammatory cells,vascular smooth muscle cells(VSMCs)and connective tissue within the arterial intima.Epidemiological studies have shown that high-density lipoprotein cholesterol(HDL-C)is inversely proportional to the risk of cardiovascular disease.The anti-atherogenic effect of HDL is in part via reverse cholesterol transport(RCT),a pathway that transports excess cholesterol from peripheral tissues to the liver,which is a major anti-atherosclerosis mechanism.Cyclodextrins(CDs)are cyclic oligosaccharides composed of 6,7,or 8 glucopyranosides,called α-,β-and γ-CD,respectively.HPβCD is a hydroxypropyl derivative of β-CD.Clinical and animal model studies have demonstrated that HPβCD forms a complex with cholesterol and reduces the content of cholesterol crystals(CCS)in atherosclerotic plaques.However,the effect of HPβCD on the progression of atherosclerosis is unclear.Therefore,our study evaluated the effects of HPβCD on atherosclerosis in rabbits using blood lipids,atherosclerotic plaque formation,and inflammatory responses.To investigate the therapeutic effects of cyclodextrin on the development of atherosclerosis in rabbits,we evaluated the effects of(2-hydroxypropyl)-β-cyclodextrin(HPβCD)therapy on the organ coefficient,lipid profiles,inflammatory cytokines and atherosclerotic plaques in rabbits fed a high-fat diet.Our results demonstrated that HPβCD therapy reduced plasma triglyceride levels and inflammatory cytokine levels but increased plasma HDL-C levels,the total cholesterol(TC)and low-density lipoprotein cholesterol(LDL-C)were slightly decreased without a significant difference.HPβCD therapy produced a significant decrease in the atherosclerotic lesion area and reduced macrophage and collagen content in the lesions.The expression levels of inflammatory genes in plasma and aortic plaques were significantly reduced by HPβCD treatment,but the expression of ATP-binding cassette(ABC)transporters A1(ABCA1)and G1(ABCG1)in aortic plaques and livers increased significantly.HPβCD therapy may produce additional anti-atherosclerotic benefits likely via increasing HDL-C levels.