Study On The Relationship Between Lipoprotein(a) And Coronary Heart Disease In Guangxi Zhuang Population And The Mechanism Research

Objective(1)To observe the correlation of lipoprotein(a)levels and c oronary heart disease in Guangxi Zhuang population;(2)To investigate the influ ence of lipoprotein(a)and oxidized lipoprotein(a)on macrophages autophagy,pr eliminary study the effect of macrophage autophagy in atherosclerosis induced b y oxidized lipoprotein(a)and lipoprotein(a).Methods 1.Serum was collected of 180 patients with coronary heart disease(CHD)and 54 patients without CHD in Guangxi zhuang population,dete cted the serum lipoprotein(a)levels by ELISA,analyze the correlation between t he levels of lipoprotein(a)and CHD in Guangxi Zhuang population.2.Firstly,lip oprotein(a)was oxidized,THP-1 cells were induced by PMA to differentiate int o macrophages;secondly,THP-1 macrophages were treated with different conce ntrations of lipoprotein(a)and oxidized lipoprotein(a);finally,mRFP-GFP-LC3 double fluorescence was used to dectect the autophagy changes,electron micros copy was used to observe the formation of autophagybody,real-time quantitativ e PCR was used to dectect the expression levels of autophagy marker gene Becli n1 mRNA and PI3K-Akt-mTOR signal passway relative mRNA expression leve Is,western blot was used to dectect the expression level of Beclin1,LC3,and PI 3K-Akt-mTOR signal passway relative proteins,we observe the effects of autoph agy changes,to preliminary study the effect of macrophage autophagy in atheros clerosis induced by oxidized lipoprotein(a)and lipoprotein(a).Results 1.The levels of LP(a)in patients with CHD is higher than tha t without CHD patients in Guangxi Zhuang population,the difference is statistic ally significant(P<0.01);there are no differences between CHD patients,the difference was not statistically significant(P>0.05).2.The correlation betwee n Lp(a)and clinical indexes was analyzed after controlling for age,sex and BM I,the difference was not statistically significant(P>0.05);3.Ordinal logistic r egression analysis showed that LP(a)is a risk factor for coronary heart disease(OR=1.031,P<0.001)in Guangxi Zhuang population;4.mRFP-GFP-LC3 Double fluorescence tracing and transmission electron microscopy showed that,Ox-lp(a)promotes autophagy in THP-1 macrophages,LP(a)down regulate the level of autophagy in THP-1 macrophages.5.qPCR shows that,treated with ox-LP(a),the Beclinl mRNA was higher than that of control group,the difference was statistically significant(P<0.001 or P<0.05);PI3K-Akt-mTOR signalin g pathway related genes p85,mTOR mRNA was higher than that of control grou p,the difference was statistically significant(P<0.001 or P<0.05),while Ak t mRNA was no differences;treated with LP(a),Beclin1 mRNA was not statistic ally significant compared with that of the control group(P>0.05);the expres sion of p85,Akt,mTOR mRNA showed no obvious change,compare with the co ntrol group,the difference was not statistically significant(P<0.001).6.WB t est shows that,treated with ox-LP(a),the expression of Beclin1 protein increase d,the difference was statistically significant compared with that of the control gr oup;the expression of 1c3 protein increased,but the difference was not statisticall y significant between groups;the expression of p85,Akt,mTOR and p-mTOR p rotein increased,compared with the blank control group,the difference was stati stically significant;treated with LP(a),their was no difference of Beclin1 and LC 3 proteins compared with the control group.Conclusion 1.Lipoprotein(a)concentration is associated with CHD as a risk factor in Guangxi zhuang population.2.lipoprotein(a)activated PI3K-Akt-mTOR pathway and inhibit autophagy in THP-1 macrophages;Oxidized lip oprotein(a)activated PI3K-Akt-mTOR autophagy pathway,oxidized lipoprotein(a)may inhibit autophagy in THP-1 macrophages.