Plasma proteomic analysis of association between atrial fibrillation, coronary microvascular disease and heart failure.

IF 1.3
Gunjan Dixit, John Blair, Cevher Ozcan
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Abstract

The clinical association between atrial fibrillation (AF), coronary microvascular disease (CMD) and heart failure with preserved ejection fraction (HFpEF) is highly prevalent, however the mechanism behind this association is not known. We hypothesized that plasma proteomic analysis can identify novel biomarkers and the mechanistic pathways in concomitant AF, CMD and HFpEF. To discover circulating biomarkers for the association between AF, CMD and HFpEF, an unbiased label-free quantitative proteomics approach was used in plasma derived from patients who underwent coronary physiology studies (n=18). Circulating proteins were analyzed by liquid chromatography-mass spectrometry and screened to determine candidate biomarkers of the concomitant AF, CMD and HFpEF. We identified 130 dysregulated proteins across the groups with the independent patient replicates. Among those, 35 proteins were candidate biomarkers of the association between AF, CMD and HFpEF. We found significantly elevated SAA1, LRG1 and APOC3 proteins in the coexistence of AF, CMD and HFpEF, whereas LCP1, PON1 and C1S were markedly downregulated in their associations. AF was associated with reduced LCP1, KLKB1 and C4A in these patients. Combined downregulation of PON1 and C1S was a marker of concurrent HFpEF and CMD. PON1 was associated with HFpEF while C1S was a marker of CMD. These proteins are related to inflammation, extra cellular remodeling, oxidative stress, and coagulation. In conclusion, plasma proteomic profile provides biomarkers and mechanistic insight into the association of AF, CMD and HFpEF. SAA1, LRG1, APOC3, LCP1, PON1 and C1S are candidate markers for the risk stratification of their associations and potential underlying mechanistic pathways.

血浆蛋白质组学分析心房颤动、冠状动脉微血管疾病和心力衰竭的关系。
心房颤动(AF)、冠状动脉微血管疾病(CMD)和心力衰竭伴保留射血分数(HFpEF)之间的临床关联是非常普遍的,但这种关联背后的机制尚不清楚。我们假设血浆蛋白质组学分析可以识别AF、CMD和HFpEF合并的新的生物标志物和机制途径。为了发现AF、CMD和HFpEF之间关联的循环生物标志物,对接受冠状动脉生理学研究的患者(n=18)的血浆使用了一种无偏见的无标记定量蛋白质组学方法。采用液相色谱-质谱联用技术分析循环蛋白,筛选并发AF、CMD和HFpEF的候选生物标志物。我们通过独立的患者重复鉴定了130个不同组的失调蛋白。其中,35个蛋白是AF、CMD和HFpEF之间关联的候选生物标志物。我们发现,在AF、CMD和HFpEF共存的情况下,SAA1、LRG1和APOC3蛋白显著升高,而LCP1、PON1和C1S在它们的关联中显著下调。在这些患者中,房颤与LCP1、KLKB1和C4A降低相关。PON1和C1S的联合下调是并发HFpEF和CMD的标志。PON1与HFpEF相关,而C1S是CMD的标志物。这些蛋白与炎症、细胞外重塑、氧化应激和凝血有关。总之,血浆蛋白质组学分析为房颤、CMD和HFpEF的关联提供了生物标志物和机制见解。SAA1, LRG1, APOC3, LCP1, PON1和C1S是其关联和潜在机制途径的风险分层的候选标记物。
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来源期刊
American journal of cardiovascular disease
American journal of cardiovascular disease CARDIAC & CARDIOVASCULAR SYSTEMS-
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