血浆前蛋白转化酶枯草溶菌素9与钙化性主动脉瓣疾病的关联机制

Association mechanism of plasma protein convertase subtilisin/Kexin type 9 and calcific aortic valve disease

目的:探讨血浆前蛋白转化酶枯草溶菌素9(PCSK9)与钙化性主动脉瓣疾病(CAVD)的相关性。方法:经心脏彩超筛选CAVD患者120例及阴性对照组患者40例,通过CT定量评分系统分4组:AVC 1、2、3和4级,并通过软件计算主动脉瓣钙化积分。检测血浆总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、三酰甘油(TG)、载脂蛋白A1(Apo A1)及载脂蛋白B(Apo B)、脂蛋白(a){LP(a)}和高敏C反应蛋白(hs CRP)水平以及PCSK9水平。结果:4组患者LDL-C、Apo B和Lp(a)水平差异有显著性(P<0.05),AVC2-4级患者明显高于AVC1级,而TG、HDL-C、apo A1和hs CRP组间差异无统计学意义。AVC3级和AVC 4级的TC水平高于AVC1组(P<0.05)。同时,AVC2-4组血浆PCSK9水平高于AVC1组(P<0.05)。将所有人群的主动脉瓣钙化积分与TC(r=0.248,P=0.026),LDL-C(r=0.222,P=0.048),Lp(a)(r=0.276,P=0.013),Apo A1(r=0.245,P=0.012),Apo B(r=0.212,P=0.019)和PCSK9(r=0.309,P=0.005)均存在明显相关性,Apo A1,Apo B呈正相关。结论:CAVD患者PCSK9水平明显高于对照组,PCSK9与CAVD的发生存在相关性。

Objective:To evaluate the association between the level of plasma proprotein convertase subtilisin/Kexin 9(PCSK9)with incidence and severity of calcified aortic valve disease(CAVD).Methods:We prospectively recruited 120 CAVD patients with at least increased echo density and 40 control patients by transthoracic echocardiography.All patients were grouped by CT quantitative scoring system:aortic valve calcification(AVC)1,2,3 and 4.Calcium score of aortic valve were calculated.Total cholesterol(TC),low density lipoprotein cholesterol(LDL-C),high density lipoprotein cholesterol(HDL-C),triglyceride(TG),carrying lipoprotein A1(apo A1)and apolipoprotein B(apo B),lipoprotein(a){LP(a)}and hypersensitive C-reactive protein(hsCRP)were detected by biochemical analyzer.Plasma PCSK9 levels were measured by enzyme-linked immunosorbent assay.The relationship between AVC and plasma PCSK9 level,blood lipid,Apo A1,Apo B and hsCRP was analyzed.Results:The data indicated that Apo,B Lp(a)and LDL-C levels in AVC2-4 level was significantly higher than that of AVC1(P<0.05),while TG,APO,A1 HDL-C and hsCRP were not different significantly in the four groups.The levels of TC in group AVC3 and AVC4 were significantly higher than those in group AVC1(P<0.05).At the same time,the patients of grade AVC2-4 have higher level of plasma PCSK9 than patients of group AVC1(P<0.05).Correlation analysis was performed and aortic valve calcium score were significantly correlated with TC(r=0.248,P=0.026),LDL-C(r=0.222,P=0.048),Lp(a)(r=0.276,P=0.013),Apo A1(r=0.245,P=0.012),Apo B(r=0.212,P=0.019)and PCSK9(r=0.309,P=0.005)in all study subjects.PCSK9 was positively correlated with TC,LDL,LP(a),Apo A1,Apo,and no correlation with hsCRP(B).Conclusion:The level of PCSK9 in CAVD patients was significantly higher than that in control group.And there is an association of PCSK9 levels with the presence of CAVD,however.