Dataset Information

CTMM Circulating Cells: Granulocytes in chronic total coronary occlusion

ABSTRACT: 90 min LC-MS/MS run of granulocyte digest (control)

INSTRUMENT(S): LTQ Orbitrap Velos, instrument model, Agilent instrument model

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Granulocyte

SUBMITTER: O Bleijerveld

PROVIDER: PRD000684 | Pride | 2013-02-19

REPOSITORIES: Pride

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	PRIDE_Exp_Complete_Ac_22507.pride.mgf.gz	Mgf
	PRIDE_Exp_Complete_Ac_22507.xml.gz	Xml
	PRIDE_Exp_Complete_Ac_22508.pride.mgf.gz	Mgf
	PRIDE_Exp_Complete_Ac_22508.xml.gz	Xml
	PRIDE_Exp_Complete_Ac_22509.pride.mgf.gz	Mgf

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Publications

Deep proteome profiling of circulating granulocytes reveals bactericidal/permeability-increasing protein as a biomarker for severe atherosclerotic coronary stenosis.

Bleijerveld Onno B OB Wijten Patrick P Cappadona Salvatore S McClellan Elizabeth A EA Polat Ayse N AN Raijmakers Reinout R Sels Jan-Willem JW Colle Loes L Grasso Simona S van den Toorn Henk W HW van Breukelen Bas B Stubbs Andrew A Pasterkamp Gerard G Heck Albert J R AJ Hoefer Imo E IE Scholten Arjen A

Journal of proteome research 20121011 11

Coronary atherosclerosis represents the major cause of death in Western societies. As atherosclerosis typically progresses over years without giving rise to clinical symptoms, biomarkers are urgently needed to identify patients at risk. Over the past decade, evidence has accumulated suggesting cross-talk between the diseased vasculature and cells of the innate immune system. We therefore employed proteomics to search for biomarkers associated with severe atherosclerotic coronary lumen stenosis i ...[more]

PMID: 23020738

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Project description:IntroductionThe pathophysiology of coronary chronic total occlusion (CTO) has not been fully elucidated.MethodsIn 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. We performed enzyme-linked immunosorbent assay (ELISA) to further confirm the common DEPs in the two-group comparisons (CON vs. CTO and CTO vs. CTO-PCI).ResultsA 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, we generated a Venn diagram to identify the common DEPs in the two-group comparisons. 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, moreover, CSF1 and LGALS1 were validated via ELISA.ConclusionsThe results of this study reveal a dynamic pattern of the molecular response after CTO vessel immediate reperfusion, and identified seven proteins which would be the potential targets for novel therapeutic strategies to prevent coronary CTO.

Project description:Background: Circular RNA (circRNA) has been reported to be involved in the pathogenesis of cardiovascular disease (CVD), however, it is unclear whether circRNA carried by exosomes (exos) can be used as biomarkers for chronic coronary syndrome (CCS). This study aimed to investigate the expression pattern of exosomal circRNAs in the plasma of CCS patients, and to screen exo-circRNAs that can act as biomarkers for the diagnosis of CCS. Methods: High-throughput sequencing technology was carried out in the plasma exosomal RNA of 15 CCS patients and 15 non-cardiac chest pain patients (NCCP, control group) (sequencing cohort) to screen for differentially expressed circRNAs. Selected differentially expressed exo-circRNAs were further verified by real time polymerase chain reaction (RT-PCR) in a small-sample cohort (derivation cohort) and a large-sample cohort (validation cohort). Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic value of exo-circRNAs for CCS patients. Results: By high-throughput sequencing of circRNAs in 15 CCS patients and 15 NCCP patients, 276 circRNAs differentially expressed in plasma exosomes of CCS patients were screened by using |log2(Fold change) |>1 and q-value<0.001, and 103 were up-regulated and 173 were down-regulated. Among the 103 up-regulated circRNAs, 5 circRNAs with high expression levels and significantly increased in plasma exosomes of CCS patients were selected for validation. Twice RT-PCR validation demonstrated that exo-hsa_circ_0075269 and exo-hsa_circ_0000284 were significantly up-regulated in patients with CCS (P<0.001). Circulating exo-hsa_circ_0075269 and exo-hsa_circ_0000284 yielded the area under the curve (AUC) values of 0.761 (P<0.001, 95%CI=0.669, 0.852) and 0.623 (P=0.015, 95%CI=0.522, 0.724) for CCS, respectively by ROC curve analysis. Moreover, AUC of hsa_circ_0075269 combined with hsa_circ_0000284 for diagnosing CCS was 0.741 (P<0.001, 95%CI=0.667, 0.850). Conclusion: The expression profile of circRNA in plasma exosomes of patients with CCS was significantly different from that of the control group. Plasma exo-hsa_circ_0075269 and exo-hsa_circ_0000284 have the potential to be new biomarkers for CCS diagnosis.