scholarly journals Discovery of plasma biomarkers for predicting the severity of coronary artery atherosclerosis by quantitative proteomics

2020 ◽  
Vol 8 (1) ◽  
pp. e001152 ◽  
Author(s):  
Eu Jeong Ku ◽  
Kyung-Cho Cho ◽  
Cheong Lim ◽  
Jeong Won Kang ◽  
Jae Won Oh ◽  
...  

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.

2002 ◽  
Vol 25 (4) ◽  
pp. 154-160 ◽  
Author(s):  
Koichi Kawano ◽  
Hideaki Yoshino ◽  
Nobuo Aoki ◽  
Hiroshi Udagawa ◽  
Atsushi Watanuki ◽  
...  

2015 ◽  
Vol 115 ◽  
pp. S97
Author(s):  
Cengiz Ozturk ◽  
Mustafa Aparci ◽  
Ali Osman Yıldırım ◽  
Sait Demirkol ◽  
Murat Unlu ◽  
...  

2004 ◽  
Vol 128 (11) ◽  
pp. 1263-1266
Author(s):  
Michele T. Stauffenberg ◽  
Richard A. Lange ◽  
L. David Hillis ◽  
Joaquin Cigarroa ◽  
Rebecca M. Hsu ◽  
...  

Abstract Context.—Homocysteine is emerging as a novel marker of atherothrombosis. Its role as an independent risk factor for cardiovascular disease is generally accepted. There is scanty data correlating homocysteine levels measured by immunoassay with cardiovascular disease. We previously validated a fluorescence polarization immunoassay for measuring homocysteine, which compared favorably with high performance liquid chromatography. Objective.—To determine if homocysteine levels measured by immunoassay correlate with extent of atherosclerotic burden, as represented by degree of coronary artery stenosis determined by coronary angiography. Design.—Fasting plasma samples were obtained from patients undergoing coronary angiography (N = 165). Homocysteine levels were measured by immunoassay and coronary artery stenosis was determined by coronary angiography. Results.—Median coronary artery stenosis for the 3 homocysteine subgroups, less than 1.35, 1.35 to 6.75, and greater than 6.75 mg/L (<10, 10–15, and >15 μmol/L), was 75%, 90%, and 99%, respectively (P = .01 for trend). Also, folate and vitamin B12 levels decreased with increasing homocysteine levels (P = .01 and .04, respectively, for trend). Spearman's correlation showed a significant association between homocysteine level and coronary artery stenosis (r = 0.20; P = .009). When men and women were examined separately, the correlation was significant only for women (r = 0.30; P = .01). Conclusion.—Homocysteine levels, as measured by immunoassay, show a positive correlation with cardiovascular disease in women. Thus, this is a valid measure of atherosclerotic burden and, therefore, a reliable addition to the established laboratory repertoire for the assessment of cardiovascular disease.


2019 ◽  
Vol 68 (5) ◽  
pp. 542-545
Author(s):  
Shingo Kunioka ◽  
Hiroto Kitahara ◽  
Seima Ohira ◽  
Yuki Tada ◽  
Nobuyuki Akasaka ◽  
...  

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Ting Sun ◽  
Wanlin Zhan ◽  
Lijiang Wei ◽  
Zuojun Xu ◽  
Li Fan ◽  
...  

Abstract Background We investigated the role of ANGPTL3 and ANGPTL4 in atherosclerosis development and determined whether plasma concentrations of ANGPTL3 and ANGPTL4 are related to the degree of coronary stenosis. Methods A total of 305 consecutive patients with angina who underwent diagnostic coronary angiography were enrolled in the study between August 2017 and August 2018. The levels of ANGPTL3 and ANGPTL4 were measured by using competitive ELISA kits. Results According to the degree of coronary artery stenosis, patients were classified into four types: coronary artery stenosis of < 10%, 10-50%, 50-75, and > 75%. The plasma ANGPTL3 level was higher (51.71 ± 52.67 vs. 24.65 ± 10.32 ng/mL, P < 0.001) and that of ANGPTL4 was lower (454.66 ± 269.05 vs. 875.49 ± 961.15 ng/mL, P < 0.001) in the coronary artery stenosis ≥ 10% group than in the < 10% group. ANGPTL3 and ANGPTL4 levels were significantly associated with the severity of coronary vascular stenosis. ROC curve analyses indicated that ANGPTL3 concentrations above 30.5 ng/mL can predict atherosclerosis with a sensitivity of 71.2% and specificity of 75.3%, and that ANGPTL4 levels below 497.5 ng/mL can predict atherosclerosis with a sensitivity of 63.9% and specificity of 74.5%. ANGPTL3 and ANGPTL4 were determined to be independent risk factors for coronary atherosclerosis with odds ratios (ORs) of 0.189 (95% CI 0.097-0.368, P < 0.001) and 3.625 (95% CI 1.873-7.016, P < 0.001), respectively. Conclusions Increased ANGPTL3 or decreased ANGPTL4 shows an association with coronary atherosclerosis and, may become a predictor of coronary atherosclerosis in the future.


2019 ◽  
Vol 71 (4) ◽  
pp. 655-663
Author(s):  
Gordana Milic ◽  
Jasna Gacic ◽  
Ana Mladenovic-Markovic ◽  
Ivan Soldatovic ◽  
Dragan Matic ◽  
...  

Individuals with type 1 diabetes have an increased risk of premature atherosclerosis. The aim of this study was to evaluate the possible predictive significance of elevated plasma total homocysteine (tHcy), lower serum 25-hydroxy vitamin D (25(OH)D) concentrations and increased carotid intima-media thickness (CIMT) for the development of coronary atherosclerosis in patients with type 1 diabetes mellitus (T1D) and no previous history of ischemic heart disease. The study included 73 patients previously diagnosed with T1D. The patients were divided into groups with and without non-obstructive moderate coronary artery stenosis. Coronary artery stenosis was examined using coronary multidetector computed tomographic angiography (MDCTA); CIMT was measured by B-mode ultrasound. The patients with moderate stenosis had significantly higher HbA1c (p<0.001), elevated tHcy (p<0.001), increased CIMTmax. (p<0.001) but lower 25(OH)D (p<0.001) in comparison to patients without detectable coronary atherosclerosis. Homocysteine (AUCHcy=0.955; p<0.001), vitamin D (AUCvit D=0.792; p<0.001) and CIMT max (AUCCIMT=0.743; p<0.001) (AUC or area under the curve) appear to be adequate markers for detecting stenosis of coronary arteries using receiver operating characteristic (ROC) curve analysis. Multivariate logistic regression analysis showed that serum homocysteine was the only significant predictor of moderate coronary artery stenosis. Our study implies that tHcy can be used as a reliable predictor of coronary artery atherosclerosis in patients with T1D. 25(OH)D and CIMT can also be used, but with lower diagnostic accuracy.


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