结合质谱法和孟德尔随机化的脂蛋白(a)与低密度脂蛋白蛋白质组学图谱的比较分析
A Comparative Analysis of the Lipoprotein(a) and Low-Density Lipoprotein Proteomic Profiles Combining Mass Spectrometry and Mendelian Randomization.
作者信息
Bourgeois Raphaëlle, Girard Arnaud, Perrot Nicolas, Guertin Jakie, Mitchell Patricia L, Couture Christian, Gotti Clarisse, Bourassa Sylvie, Poggio Paolo, Mass Elvira, Capoulade Romain, Scipione Corey A, Després Audrey-Anne, Couture Patrick, Droit Arnaud, Pibarot Philippe, Boffa Michael B, Thériault Sébastien, Koschinsky Marlys L, Mathieu Patrick, Arsenault Benoit J
机构信息
Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec, Quebec, Canada.
Department of Medicine, Faculty of Medicine, Université Laval, Quebec, Canada.
出版信息
CJC Open. 2020 Dec 3;3(4):450-459. doi: 10.1016/j.cjco.2020.11.019. eCollection 2021 Apr.
BACKGROUND
Lipoprotein(a) (Lp[a]), which consists of a low-density lipoprotein (LDL) bound to apolipoprotein(a), is one of the strongest genetic risk factors for atherosclerotic cardiovascular diseases. Few studies have performed hypothesis-free direct comparisons of the Lp(a) and the LDL proteomes. Our objectives were to compare the Lp(a) and the LDL proteomic profiles and to evaluate the effect of lifelong exposure to elevated Lp(a) or LDL cholesterol levels on the plasma proteomic profile.
METHODS
We performed a label-free analysis of the Lp(a) and LDL proteomic profiles of healthy volunteers in a discovery (n = 6) and a replication (n = 9) phase. We performed inverse variance weighted Mendelian randomization to document the effect of lifelong exposure to elevated Lp(a) or LDL cholesterol levels on the plasma proteomic profile of participants of the INTERVAL study.
RESULTS
We identified 15 proteins that were more abundant on Lp(a) compared with LDL (, , , , , , , , , , , , , , and ). We found no proteins that were more abundant on LDL compared with Lp(a). After correction for multiple testing, lifelong exposure to elevated LDL cholesterol levels was associated with the variation of 18 plasma proteins whereas Lp(a) did not appear to influence the plasma proteome.
CONCLUSIONS
Results of this study highlight marked differences in the proteome of Lp(a) and LDL as well as in the effect of lifelong exposure to elevated LDL cholesterol or Lp(a) on the plasma proteomic profile.
背景
脂蛋白(a)（Lp[a]）由与载脂蛋白(a)结合的低密度脂蛋白（LDL）组成，是动脉粥样硬化性心血管疾病最强的遗传风险因素之一。很少有研究对Lp(a)和LDL蛋白质组进行无假设的直接比较。我们的目标是比较Lp(a)和LDL的蛋白质组学图谱，并评估终生暴露于升高的Lp(a)或LDL胆固醇水平对血浆蛋白质组学图谱的影响。
方法
我们在探索阶段（n = 6）和验证阶段（n = 9）对健康志愿者的Lp(a)和LDL蛋白质组图谱进行了无标记分析。我们进行了逆方差加权孟德尔随机化，以记录终生暴露于升高的Lp(a)或LDL胆固醇水平对INTERVAL研究参与者血浆蛋白质组图谱的影响。
结果
我们鉴定出15种在Lp(a)上比在LDL上更丰富的蛋白质（、、、、、、、、、、、、、、和）。我们未发现有蛋白质在LDL上比在Lp(a)上更丰富。在进行多重检验校正后，终生暴露于升高的LDL胆固醇水平与18种血浆蛋白的变化有关^{[1]}，而Lp(a)似乎并未影响血浆蛋白质组。
结论
本研究结果突出了Lp(a)和LDL蛋白质组的显著差异，以及终生暴露于升高的LDL胆固醇或Lp(a)水平对血浆蛋白质组图谱的影响。
Zotero 插件