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Discovery of plasma biomarkers for predicting the severity of coronary artery atherosclerosis by quantitative proteomics
- Source :
- BMJ Open Diabetes Research & Care, Vol 8, Iss 1 (2020), BMJ Open Diabetes Research & Care
- Publication Year :
- 2020
- Publisher :
- BMJ Publishing Group, 2020.
-
Abstract
- IntroductionCardiovascular disease (CVD) in patients with diabetes is the leading cause of death. Finding early biomarkers for detecting asymptomatic patients with CVD can improve survival. Recently, plasma proteomics—targeted selected reaction monitoring/multiple reaction monitoring analyses (MRM)—has emerged as highly specific and sensitive tools compared with classic ELISA methods. The objective was to identify differentially regulated proteins according to the severity of the coronary artery atherosclerosis.Research design and methodsA discovery cohort, a verification cohort and a validation cohort consisted of 18, 53, and 228 subjects, respectively. The grade of coronary artery stenosis was defined as a percentage of luminal stenosis of the major coronary arteries. Participants were divided into six groups, depending on the presence of diabetes and the grade of coronary artery stenosis. Two mass spectrometric approaches were employed: (1) conventional shotgun liquid chromatography tandem mass spectrometry for a discovery and (2) quantitative MRM for verification and validation. An analysis of the covariance was used to examine the biomarkers’ predictivity beyond conventional cardiovascular risks.ResultsA total of 1349 different proteins were identified from a discovery cohort. We selected 52 proteins based on the tandem mass tag quantitative analysis then summarized as follows: chemokine (C-X-C motif) ligand 7 (CXCL7), apolipoprotein C-II (APOC2), human lipopolysaccharide-binding protein (LBP) and dedicator of cytokinesis 2 (DOCK2) in diabetes; CXCL7, APOC2, LBP, complement 4A (C4A), vitamin D-binding protein (VTDB) and laminin β1 subunit in non-diabetes. Analysis of covariance showed that APOC2, DOCK2, CXCL7 and VTDB were upregulated and C4A was downregulated in patients with diabetes showing severe coronary artery stenosis. LBP and VTDB were downregulated in patients without diabetes, showing severe coronary artery stenosis.ConclusionWe identified significant associations between circulating APOC2, C4A, CXCL7, DOCK2, LBP and VTDB levels and the degree of coronary artery stenosis using the MRM technique.
- Subjects :
- Proteomics
Cardiovascular and Metabolic Risk
medicine.medical_specialty
Apolipoprotein B
Endocrinology, Diabetes and Metabolism
030209 endocrinology & metabolism
Coronary Artery Disease
Type 2 diabetes
Asymptomatic
Diseases of the endocrine glands. Clinical endocrinology
Coronary artery disease
03 medical and health sciences
0302 clinical medicine
Internal medicine
Diabetes mellitus
Humans
Medicine
030212 general & internal medicine
biology
business.industry
biomarkers
Atherosclerosis
proteomic analysis
medicine.disease
RC648-665
Coronary arteries
Stenosis
medicine.anatomical_structure
Cohort
biology.protein
Cardiology
type 2 diabetes
medicine.symptom
business
Subjects
Details
- Language :
- English
- ISSN :
- 20524897
- Volume :
- 8
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- BMJ Open Diabetes Research & Care
- Accession number :
- edsair.doi.dedup.....91eeb1be261fd77b85632d80863739bf