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ITIH4: A New Potential Biomarker of "Toxin Syndrome" in Coronary Heart Disease Patient Identified with Proteomic Method.

ABSTRACT: Objective. This trial aims to look for the protein biomarker of "toxin syndrome" of CHD patients. Methods. We have performed two trials in this paper. The first trial was a randomized controlled trial (RCT) of the plasma proteome in unstable angina (UA) patients by Maldi-Tof Mass. The second trial was a nested case-control study in 1503 stable CHD patients with one-year followup for acute cardiovascular events (ACEs). Results. In the RCT study, 12 protein spots were found to be the differential protein for the significant differences between the difference of before and after treatment in group A and group B; 2 of them (3207.37?Da and 4279.95?Da) was considered to be unique to "toxin syndrome" for being differential proteins of group B but not group A. These 2 spots were identified as Isoform 1 of Fibrinogen alpha chain precursor (FGA, 3207.37?Da) and Isoform 2 of inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4, 4279.95?Da), respectively. In the nested case-control study, the result of Western blot demonstrated that protein expression of ITIH4 in the group with followup ACEs was significantly lower than the matched group without followup ACEs (P = 0.027). Conclusion. ITIH4 might be a new potential biomarker of CHD "toxin syndrome" in TCM, indicating the potential role in early identifying high-risk CHD patients in stable period.

SUBMITTER: Xu H

PROVIDER: S-EPMC3760120 | biostudies-other | 2013

REPOSITORIES: biostudies-other

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ITIH4: A New Potential Biomarker of "Toxin Syndrome" in Coronary Heart Disease Patient Identified with Proteomic Method.

Xu Hao H Shang Qinghua Q Chen Hao H Du Jianpeng J Wen Jianyan J Li Geng G Shi Dazhuo D Chen Keji K

Evidence-based complementary and alternative medicine : eCAM 20130819

Objective. This trial aims to look for the protein biomarker of "toxin syndrome" of CHD patients. Methods. We have performed two trials in this paper. The first trial was a randomized controlled trial (RCT) of the plasma proteome in unstable angina (UA) patients by Maldi-Tof Mass. The second trial was a nested case-control study in 1503 stable CHD patients with one-year followup for acute cardiovascular events (ACEs). Results. In the RCT study, 12 protein spots were found to be the differential ...[more]

PMID: 24023573

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Project description:BackgroundThe present study aimed at using a proteomics based approach to: a) analyze and contrast the proteome of the healthy and isoproterenol induced hypertrophied hearts and b) identify potential biomarkers for diagnosis of cardiac hypertrophy.MethodsMale Sprague Dawley (SD) rats were administered isoproterenol (ISO, 5 mg/kg, sc, once daily) for 14 days to induce cardiac hypertrophy. There was a significant (p<0.05) increase (~ 55%) in the heart weight to tail length ratio after 14 days of treatment and cardiac hypertrophy was evidenced by significant increase of β-MHC and ANP, two indicative markers of cardiac hypertrophy, in the treated heart compared to that of control. Following confirmation of hypertrophy, 2DE of the tissue samples was done followed by MS/MS analysis of the protein spots to obtain a proteomic view for identification of novel biomarkers.ResultsSeveral important proteins were identified by proteomics analysis. They belong to the major functional categories such as cholesterol and protein metabolism, muscle contraction and development, transport, TCAcycle, ATP-biosynthesis, chaperone, signal transduction, DNA synthesis and ubiquitinisation. Careful examination of these protein spots by image analysis led to the successful identification of 7 differentially expressed proteins in the diseased sample. Further extension of this work for validation of differential expression of these proteins was also achieved by RTPCR and western blotting.ConclusionsOur results demonstrate characteristic protein expression profile in control and hypertrophy condition in SD rats and also expand the existing knowledge on differentially expressed proteins in hypertrophy. The study signifies the importance of reduced expression of a novel protein such as Prohibitin (PHB) which may be associated with the cardiomyocytes growth and cardiac hypertrophy. However, further work is necessary to confirm the role of PHB in human heart and its potential role in diagnostic and therapeutic intervention in the clinic.

Project description:BackgroundSoluble programmed cell death-ligand 1 (sPD-L1) has been well documented to activate immunosuppression and is considered an essential predictor of negative clinical outcomes for several malignances and inflammatory conditions. However, the clinical significance of sPD-L1 in the peripheral blood of patients with coronary artery disease (CAD) remains unclear. The aim of this study was to assess the correlations of sPD-L1 with clinical features in CAD patients and evaluate the diagnostic value of this protein in CAD.MethodsA total of 111 CAD patients and 97 healthy volunteers who served as healthy controls (HCs) were consecutively enrolled. Plasma levels of sPD-L1 were measured with an amplified enzyme-linked immunosorbent assay (ELISA), and hs-CRP was measured with a C-reactive protein assay kit. The levels of other inflammatory cytokines were assessed in 88 CAD patients and 47 HCs by a multiparameter immunoluminescence flow cytometry detection technique. A logistic regression model was used to assess the independent association of sPD-L1 with acute coronary syndrome (ACS). The correlation between sPD-L1 and inflammatory cytokines in ACS was also assessed.ResultsPlasma levels of sPD-L1 were significantly increased in CAD patients, especially those with ACS. Univariate logistic regression analysis revealed that sPD-L1 (OR: 3.382, 95% CI: 2.249-5.084, p < 0.001), BMI, hypertension, diabetes, dyslipidemia, previous MI, and the levels of HDL-C, LDL-C and hs-CRP were significantly associated with ACS. sPD-L1 (OR: 3.336, 95% CI: 1.084-6.167, p = 0.001) was found to be independently and significantly associated with ACS in the subsequent multivariable logistic regression analysis. Additionally, elevated plasma sPD-L1 levels were associated with increased interleukin-6 and interleukin-8 levels in ACS patients. Receiver operating characteristic (ROC) analysis showed that the AUC of sPD-L1 for diagnosing ACS was 0.778, with a sensitivity of 73.9% and a specificity of 73.4%, which was comparable with that of the inflammatory biomarker hs-CRP.ConclusionThe plasma sPD-L1 level reflects the severity of CAD, is associated with inflammatory responses and is a potential new biomarker for the diagnosis of ACS.

Dataset Information

ITIH4: A New Potential Biomarker of "Toxin Syndrome" in Coronary Heart Disease Patient Identified with Proteomic Method.

Publications

ITIH4: A New Potential Biomarker of "Toxin Syndrome" in Coronary Heart Disease Patient Identified with Proteomic Method.

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