Deleon-Pennell Kristine Y, Ero Osasere K, Ma Yonggang, Padmanabhan Iyer Rugmani, Flynn Elizabeth R, Espinoza Ingrid, Musani Solomon K, Vasan Ramachandran S, Hall Michael E, Fox Ervin R, Lindsey Merry L
Mississippi Center for Heart Research, Department of Physiology and Biophysics, Department of Preventive Medicine and Cancer Institute, Jackson Heart Study, and Division of Cardiology, UMMC, Jackson, Mississippi 39216-4505, United States.
Research Service, G.V. (Sonny) Montgomery Veterans Affairs Medical Center, Jackson, Mississippi 39216, United States.
ACS Omega. 2019 Jan 31;4(1):1272-1280. doi: 10.1021/acsomega.8b02207. Epub 2019 Jan 15.
We hypothesized that identifying plasma glycoproteins that predict the development of heart failure following myocardial infarction (MI) could help to stratify subjects at risk. Plasma collected at visit 2 (2005-2008) from an MI subset of Jackson Heart Study participants underwent glycoproteomics and was grouped by the outcome: (1) heart failure hospitalization after visit 2 ( = 15) and (2) without hospitalization by 2012 ( = 45). Proteins were mapped for biological processes and functional pathways using Ingenuity Pathway Analysis and linked to clinical characteristics. A total of 198 glycopeptides corresponding to 88 proteins were identified (data available via ProteomeXchange with identifier PXD009870). Of these, 14 glycopeptides were significantly different between MI and MI + HF groups and corresponded to apolipoprotein (Apo) F, transthyretin, Apo C-IV, prostaglandin-D2 synthase, complement C9, and CD59 ( < 0.05 for all). All proteins were elevated in the MI + HF group, except CD59, which was lower. Four canonical pathways were upregulated in the MI + HF group ( < 0.05 for all): acute phase response, liver X receptor/retinoid X receptor, and macrophage reactive oxygen species generation. The coagulation pathway was significantly downregulated in the MI + HF group ( < 0.05). Even after adjustment for age and sex, Apo F was associated with the increased risk for heart failure (OR = 21.84; 95% CI 3.20-149.14). In conclusion, glycoproteomic profiling provided candidate early MI predictors of later progression to heart failure.
我们推测,鉴定出可预测心肌梗死(MI)后心力衰竭发生的血浆糖蛋白,有助于对有风险的受试者进行分层。在杰克逊心脏研究参与者的MI亚组中,于访视2(2005 - 2008年)采集的血浆进行了糖蛋白质组学分析,并按结局分组:(1)访视2后因心力衰竭住院(n = 15)和(2)到2012年未住院(n = 45)。使用 Ingenuity Pathway Analysis 将蛋白质映射到生物学过程和功能途径,并与临床特征相关联。共鉴定出对应于88种蛋白质的198种糖肽(数据可通过 ProteomeXchange 获取,标识符为 PXD009870)。其中,14种糖肽在MI组和MI + HF组之间存在显著差异,对应载脂蛋白(Apo)F、转甲状腺素蛋白、Apo C-IV、前列腺素-D2合成酶、补体C9和CD59(所有P < 0.05)。除CD59较低外,所有蛋白质在MI + HF组中均升高。MI + HF组中有四条典型途径上调(所有P < 0.05):急性期反应、肝X受体/视黄酸X受体和巨噬细胞活性氧生成。凝血途径在MI + HF组中显著下调(P < 0.05)。即使在调整年龄和性别后,Apo F仍与心力衰竭风险增加相关(OR = 21.84;95% CI 3.20 - 149.14)。总之,糖蛋白质组分析提供了MI后进展为心力衰竭的早期候选预测指标。