Increased sortilin and its independent effect on circulating proprotein convertase subtilisin/kexin type 9 (PCSK9) in statin-naive patients with coronary artery disease
Increased sortilin and its independent effect on circulating proprotein convertase subtilisin/kexin type 9 (PCSK9) in statin-naive patients with coronary artery disease
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在未经他汀类药物治疗的冠状动脉疾病患者中，分拣蛋白增加及其对循环前蛋白转化酶枯草杆菌蛋白酶/kexin 9 型 (PCSK9) 的独立影响。
DOI：
10.1016/j.ijcard.2016.11.064
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发表时间：
2017-01-15
影响因子：
3.5
通讯作者：
Peng, Dao-quan
中科院分区：
文献类型：
--
作者：
Hu, Die;Yang, Yang;Peng, Dao-quan
背景资料：前蛋白转化酶枯草杆菌蛋白酶/kexin 9型（PCSK 9）已被证明在低密度脂蛋白受体（LDLR）的代谢中起关键作用。分拣蛋白，由血脂异常相关基因编码。SORT 1也是脂蛋白代谢的重要调节因子。动物研究已经显示分拣蛋白在调节PCSK 9分泌中的潜在作用。方法：80例冠心病患者根据临床表现和冠状动脉造影（CAG）结果分为冠心病组（n = 43）和非冠心病组（n = 37）。结果：冠心病患者血清PCSK 9浓度为247.0（218.6317 A）ng/ml，对照组为226.6（181.6270.3）ng/ml，两组比较差异有统计学意义（P = 0.007）。未接受他汀类药物治疗的患者血清PCSK 9水平仍高于对照组[261.8（216.0，315.8）vs 221.0（176.8，260.7）ng/ml，P = 0.003]。CAD患者的循环分拣蛋白水平往往高于非CAD受试者，但仅在他汀类药物初治的CAD患者和对照组之间存在显著差异[4.96（438，657）vs 428（2.96，5.03）ng/ml，P = 0.032]。血清PCSK 9浓度与分拣素水平正相关（r = 0.37，P0.001，n = 80）。分层分析显示，非他汀类药物组（r = 0.41，P = 0.001，n = 60）和非冠心病组（r = 0.47，P = 0.004，n = 37）中，PCSK 9和sortilin的相关性较强，而在他汀类药物组和冠心病组中，二者的相关性消失。经年龄、性别、LDL-胆固醇、吸烟和CAD因素校正后的逐步多元回归分析发现，所有受试者（P = 0.01）和他汀类药物初治组（P = 0.03）的PCSK 9和分拣蛋白水平均显著升高。PCSK 9与分拣蛋白独立相关，但其相关性受到他汀类药物治疗的影响。(C)2016爱思唯尔爱尔兰有限公司版权所有。
Background: Proprotein convertase subtilisin/kexin type 9 (PCSK9) has been shown to play a crucial role in the metabolism of low density lipoprotein receptor (LDLR). Sortilin, encoded by the dyslipidemia-related gene. SORT1, is also an important regulator of lipoprotein metabolism. Animal studies have shown the potential role of sortilin in regulating secretion of PCSK9. However, the data for the relationship between serum sortilin and circulating PCSK9 in CAD patients are scarce.Methods: Eighty subjects were classified into a CAD group (n = 43) and a non-CAD group (n 37) according to their clinical conditions and the results of coronary angiography (CAG). Serum PCSK9 and sortilin levels were measured with enzyme-linked immunosorbcnt assays.Results: CAD patients had markedly greater PCSK9 concentrations than controls [247.0(218.6317A) vs 226.6(181.6270.3) ng/ml, P = 0.007]. Moreover, serum PCSK9 levels were still higher in patients not receiving statin therapy, as compared with those in the control group [261.8(216.0,315.8) vs 221.0(176.8260.7)ng/ml, P = 0.003]. Circulating sortilin tended to be higher in CAD patients than in non-CAD subjects, yet the difference is significant only between the statin-naive CAD patients and controls [4.96(438,657) vs 428(2.96,5.03) nglml, P = 0.032]. Serum PCSK9 concentrations were positively associated with sortilin levels( r = 0.37, P 0.001,n = 80). Stratified analysis showed that there was stronger correlation between PCSK9 and sortilin in non-statin group (r = 0.41, P = 0.001,n = 60) as well as in the non-CAD group (r = 0.47, P = 0.004,n = 37), whereas the correlation between them was disappeared in statin group and CAD group. Using stepwise multiple regression analysis with adjustment for age, gender, LDL-cholesterol, smoking and CAD, we found that the correlation between scrum sortilin and PCSK9 levels remained significant in all subjects (P = 0.01) as well as in statin-naive group (P = 0.03).Conclusion: Both circulating PCSK9 and sortilin levels are elevated in CAD patients. PCSK9 was independent related to sortilin, but their correlation was affected by the use of statin therapy. (C) 2016 Elsevier lreland Ltd. All rights reserved.