Effects And Mechanisms Of YKL-40 Inhibiting Macrophage Apoptosis On Exacerbating Early-Stage Atherosclerotic Plaque Progression

Objective To investigate the effect of inflammatory factor YKL40 on atherosclerotic plaque at early-stage and the potential mechanism.The results would be contributive to confirming the feasibility and effectiveness of intervening lesion progression at early-stage to prevent atherosclerosis exacerbation and severe complications.Methods IHC,Elisa and rt-PCR were used to determine the relationship between the progression of early-stage carotid plaque and the expression level of YKL40 in 21 clinical samples.The effects of YKL40 on macrophage functions were figured out by pathological,proteomics,genomics detections.Those results were repeated in Ldlr^-/-mice models of atherosclerosis and further effect were clarified the of YKL40 with its antibody on lesion progression.Furthermore,the effect of YKL40 on macrophage were confirmed in vitro experiments by FCM and TUNEL detection.The downstream target proteins regulated by YKL40 in macrophage were screened out via i Traq analysis and then verified by western blot and rt-PCR.The regulation mechanism of YKL40 was further clarified on cell line RAW264.7 transfected with si RNA by FCM and TUNEL detection.Results Part I.?1?Significantly positive correlation was determined between YKL40 and the progression of early-stage carotid atherosclerotic plaque.?2?YKL40 could suppress the apoptosis of macrophages in atherosclerotic lesion of early-stage clinical samples then lead to atherosclerosis progressing.No significant correlation was identified between atherosclerotic lesion progression of early-stage clinical samples and M1/M2 macrophage polarized phenotypes.Part II:Application of YKL40 recombinant protein would significantly suppress the apoptosis of macrophages and aggravate the atherosclerotic lesion in Ldlr^-/-mice and YKL40 antibody effectively make the reverse effect.Part III.Suppression on macrophages apoptosis of YKL40 were confirmed in vitro.YKL40 could up-regulate the expression of apoptosis inhibitor Aven to restrain the activation of apoptosis initiator Caspase-9 and then inhibiting apoptosis.Conclusion YKL40 could interfere with the cleaning of essence ingredients and lead to the lesion exacerbation in early-stage atherosclerotic lesion via inhibiting macrophages apoptosis by up-regulating the expression of apoptosis inhibitor Aven to restrain the activation of Caspase-9.