Studies On The Mechanism Of The Immune Costimulatory Factor ICOS Inhibiting Atherosclerosis

Atherosclerosis(AS)is the most common disease in cardiovascular diseases(CVD).It mainly involves coronary arteries and cerebral arteries,and is characterized by the formation of atherosclerotic plaques on the arterial intima.Vascular smooth muscle cells(VSMC)are mainly located in the arterial media,and are the main components of muscle-derived foam cells and lipid plaque fibrous caps during the formation of AS.Inducible co-stimulator(ICOS)is mainly expressed on activated T cells,which can improve the basic response of T cells to exogenous antigens.Studies have shown that ICOS is abundantly expressed in aorta containing atherosclerotic plaques and may have anti-AS effects,however the concrete mechanism of action is still unclear.This study will examine the specific mechanism of action of ICOS on AS.Objective:Taking human aortic smooth muscle cells(HASMC)as the research object,the AS model was established at the cellular level to study the effect of ICOS on HASMC lipid phagocytosis and the expression of lipid phagocytosis receptors,as well as the effect on the HASMC transcriptional profile,revealing the potential mechanism of ICOS inhibiting AS,providing new strategies for AS prevention and treatment.Methods:The atherosclerotic cell model of HASMC was constructed,and the lipid phagocytosis in HASMC stimulated by ICOS was observed by laser confocal microscopy;the main lipid phagocytosis receptors CD36 and CD36 on HASMC were detected by RT-qPCR,Western blot and cell immunofluorescence experiments.The expression of LOX-1;the transcriptional profiling of HASMC stimulated by ICOS overexpressing JurKat cells(JK-ICOS)was analyzed to analyze the effect of ICOS on the gene expression profile of HASMC.Results:1.The lipid phagocytosis effect of HASMC was obvious when Dil ox-LDL concentration was 10 μg/m L.When JK-ICOS cells and HASMC costimulation ratio was 5:5,the inhibitory effect of HASMC lipid phagocytosis was the most obvious.When the concentration of recombinant human ICOS protein(rICOS) was 1.5 μg/m L,it had the most obvious inhibitory effect on HASMC lipid phagocytosis;2.ICOS can significantly inhibit the mRNA and protein expression of CD36 on HASMC;3.Cell transcriptional profiling analysis obtained differentially expressed genes affected by ICOS on HASMC,and found that ICOS may participate in HASMC phenotype transformation by regulating PI3K/Akt signaling pathway.Conclusion:ICOS may inhibit the formation of atherosclerosis by down-regulating the expression of lipid phagocytosis receptor CD36 and affecting HASMC phenotype transformation by regulating PI3K/Akt signaling pathway.