Dataset Information

Data-Independent Acquisition Proteomics Reveals Circulating Biomarkers of Coronary Chronic Total Occlusion in Humans

ABSTRACT: The pathophysiology of chronic coronary total occlusion (CTO) has not been fully elucidated. In the present study, we aimed to investigate the potential plasma biomarkers associated with the pathophysiologic progression of CTO and identify protein dynamics in the plasma of CTO vessels immediately after successful revascularization. We quantitatively analyzed the plasma proteome profiles of controls (CON, n=10) and patients with CTO pre- and post- percutaneous coronary intervention (PCI) (CTO, n=10) by data-independent acquisition proteomics. A total of 1936 proteins with 69 differentially expressed proteins (DEPs) were detected in the plasma of patients with CTO through quantitative proteomics analysis. For all these DEPs, gene ontology (GO) analysis and protein-protein interaction (PPI) analysis were performed. The results showed that most of the proteins were related to the negative regulation of proteolysis, regulation of peptidase activity, negative regulation of hydrolase activity, humoral immune response, and lipid location. Furthermore, we identified 1927 proteins with 43 DEPs in the plasma of patients with CTO vessels after immediately successful revascularization compared to pre-PCI. GO analysis revealed that the above DEPs were enriched in the biological processes of extracellular structure organization, protein activation cascade, negative regulation of response to external stimulus, plasminogen activation, and fibrinolysis. More importantly, seven proteins, ADH4, CSF1, galectin, LPL, IGF2, IgH, and LGALS1, were found to be dynamically altered in plasma during the pathophysiological progression of CTO vessels and following successful revascularization.

ORGANISM(S): Homo Sapiens

SUBMITTER: Xin Yi

PROVIDER: PXD034267 | iProX | Thu Jun 02 00:00:00 BST 2022

REPOSITORIES: iProX

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Data-independent acquisition proteomics reveals circulating biomarkers of coronary chronic total occlusion in humans.

Li Jun J Jiang Xue-Jun XJ Wang Qun-Hui QH Wu Xing-Liang XL Qu Zhe Z Song Tao T Wan Wei-Guo WG Zheng Xiao-Xin XX Yi Xin X

Frontiers in cardiovascular medicine 20221205

<h4>Introduction</h4>The pathophysiology of coronary chronic total occlusion (CTO) has not been fully elucidated.<h4>Methods</h4>In the present study, we aimed to investigate the potential plasma biomarkers associated with the pathophysiologic progression of CTO and identify protein dynamics in the plasma of CTO vessels immediately after successful revascularization. We quantitatively analyzed the plasma proteome profiles of controls (CON, <i>n</i> = 10) and patients with CTO pre- and post- perc ...[more]

PMID: 36561774

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Project description:Air pollution, especially emissions derived from traffic sources, is associated with adverse cardiovascular outcomes. However, it remains unclear how inhaled factors drive an extrapulmonary pathology, as the lung is an effective barrier for solid particulates and many gases. Previously, using plasma from healthy human subjects exposed to diesel exhaust under controlled conditions, we found that canonical inflammatory response transcripts of interleukin-8 (IL-8), intracellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) were elevated in endothelial cells treated wih plasma obtained after exposure compared with pre-exposure samples or filtered air (sham) exposures. While the findings confirmed the presence of bioactive factor(s) in the plasma after diesel inhalation, we wanted to better examine the complete genomic response to investigate 1) major responsive transcripts and 2) collected response pathways and ontogeny that may help to refine this method. Thus, we assayed previousy collected RNA with microarray chips, examining the responses of cultured endothelial cells to plasma obtained from 6 healthy human subjects exposed to 100 μg/m3 diesel exhaust or filtered air for 2 h on separate occasions. In addition to pre-exposure baseline samples, we investigated samples obtained immediately post and 24h post exposure. Primary human coronary artery endothelial cells were grown to confluence and treated with 10% plasma for 24 h, followed by isolation of RNA for microarrays. Microarray analysis of the coronary artery endothelial cells challenged with plasma identified 855 probes that change over time following diesel exhaust exposure. Over-representation analysis identified inflammatory cytokine pathways were upregulated both at the 2 and 24 h condition. These outcomes are consistent with our recent findings that plasma contains bioactive and inflammatory factors following pollutant inhalation and provide a novel pathway to explain the well-reported extrapulmonary toxicity of ambient air pollutants.

Dataset Information

Data-Independent Acquisition Proteomics Reveals Circulating Biomarkers of Coronary Chronic Total Occlusion in Humans

Publications

Data-independent acquisition proteomics reveals circulating biomarkers of coronary chronic total occlusion in humans.

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