Multivessel coronary artery disease, free fatty acids, oxidized LDL and its antibody in myocardial infarction

Груздева, О. В.; Uchasova, Evgenya; Dyleva, Yulia; Белик, Е. В.; Каретникова, В. Н.; Шилов, А А; Barbarash, O. L.

doi:10.1186/1476-511x-13-111

Cited by 26 publications

(20 citation statements)

References 19 publications

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“…It is considered one of the primary causes of disability and death from cardiovascular disease worldwide, and is a leading health threat in humans (1). AMI remains the primary cause of morbidity and mortality worldwide, with ∼7 million patients diagnosed with AMI each year (2,3). AMI continues to be the primary cause of death in 2020.…”

Section: Introductionmentioning

confidence: 99%

Predicting Diagnostic Gene Biomarkers Associated With Immune Infiltration in Patients With Acute Myocardial Infarction

Zhao

Xie

Zhang

2020

Front. Cardiovasc. Med.

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The present study was designed to identify potential diagnostic markers for acute myocardial infarction (AMI) and determine the significance of immune cell infiltration in this pathology. Methods: Two publicly available gene expression profiles (GSE66360 and GSE48060 datasets) from human AMI and control samples were downloaded from the GEO database. Differentially expressed genes (DEGs) were screened between 80 AMI and 71 control samples. The LASSO regression model and support vector machine recursive feature elimination (SVM-RFE) analysis were performed to identify candidate biomarkers. The area under the receiver operating characteristic curve (AUC) value was obtained and used to evaluate discriminatory ability. The expression level and diagnostic value of the biomarkers in AMI were further validated in the GSE60993 dataset (17 AMI patients and 7 controls). The compositional patterns of the 22 types of immune cell fraction in AMI were estimated based on the merged cohorts using CIBERSORT. Results: A total of 27 genes were identified. The identified DEGs were mainly involved in carbohydrate binding, Kawasaki disease, atherosclerosis, and arteriosclerotic cardiovascular disease. Gene sets related to atherosclerosis signaling, primary immunodeficiency, IL-17, and TNF signaling pathways were differentially activated in AMI compared with the control. IL1R2, IRAK3, and THBD were identified as diagnostic markers of AMI (AUC = 0.877) and validated in the GSE60993 dataset (AUC = 0.941). Immune cell infiltration analysis revealed that IL1R2, IRAK3, and THBD were correlated with M2 macrophages, neutrophils, monocytes, CD4 + resting memory T cells, activated natural killer (NK) cells, and gamma delta T cells. Conclusion: IL1R2, IRAK3, and THBD can be used as diagnostic markers of AMI, and can provide new insights for future studies on the occurrence and the molecular mechanisms of AMI.

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Section: Introductionmentioning

confidence: 99%

Predicting Diagnostic Gene Biomarkers Associated With Immune Infiltration in Patients With Acute Myocardial Infarction

Zhao

Xie

Zhang

2020

Front. Cardiovasc. Med.

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“…Furthermore, clinical cardiovascular studies have shown higher IgM anti-MDA-LDL levels are associated with less atherosclerotic burden and better outcomes. In contrast, studies relating IgG antibodies to CHD have been less conclusive [ [6] , [7] , [8] , [9] , [10] , [11] , [12] , [13] , [14] , [15] ].…”

Section: Introductionmentioning

confidence: 99%

IgM anti-malondialdehyde low density lipoprotein antibody levels indicate coronary heart disease and necrotic core characteristics in the Nordic Diltiazem (NORDIL) study and the Integrated Imaging and Biomarker Study 3 (IBIS-3)

et al. 2018

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BackgroundCertain immunoglobulins (Ig) are proposed to have protective functions in atherosclerosis.ObjectivesWe tested whether serum levels of IgG and IgM autoantibodies against malondialdehyde low density lipoprotein (MDA-LDL) are associated with clinical coronary heart disease (CHD) and unfavorable plaque characteristics.MethodsNORDIL was a prospective study investigating adverse cardiovascular outcomes in hypertensive patients. IBIS-3 analyzed lesions in a non-culprit coronary artery with <50% stenosis using radiofrequency intravascular ultrasound (RF-IVUS) and near-infrared spectroscopy (NIRS). Imaging was repeated after a median of 386 days on rosuvastatin. Associations of antibodies with incident CHD and imaging parameters were assessed in the two sub-studies respectively.FindingsFrom 10,881 NORDIL patients, 87 had serum sampled at baseline and developed CHD over 4.5 years, matched to 227 controls. Higher titers of IgM anti-MDA-LDL had a protective effect on adverse outcomes, with odds ratio 0.29 (0.11, 0.76; p = 0.012; p = 0.016 for trend). Therefore, the effect was explored at the lesional level in IBIS-3. 143 patients had blood samples and RF-IVUS measurements available, and NIRS was performed in 90 of these. At baseline, IgM anti-MDA-LDL levels had a strong independent inverse relationship with lesional necrotic core volume (p = 0.027) and percentage of plaque occupied by necrotic core (p = 0.011), as well as lipid core burden index (p = 0.024) in the worst 4 mm segment.InterpretationOur study supports the hypothesis that lower circulating levels of IgM anti-MDA-LDL are associated with clinical CHD development, and for the first time relates these findings to atherosclerotic plaque characteristics that are linked to vulnerability.

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“…It was suggested that lnc-KDM5D-4 was then implicated in hepatic steatosis which can occur independently of insulin resistance in the liver. Given the role of FFAs in the pathogenesis of CAD 31 – 33 , these results suggest that lnc-KDM5D-4 may play a role in the hepatic metabolism of lipids – a process of well-known relevance to atherosclerosis. Whether aberrant expression of this lincRNA plays an insignificant role in this context, or if it is a mere consequence of disease pathology remains an open question.…”

Section: Discussionmentioning

confidence: 84%

A Novel Y-Specific Long Non-Coding RNA Associated with Cellular Lipid Accumulation in HepG2 cells and Atherosclerosis-related Genes

Molina

Chew

Myers

et al. 2017

Sci Rep

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There is an increasing appreciation for the role of the human Y chromosome in phenotypic differences between the sexes in health and disease. Previous studies have shown that genetic variation within the Y chromosome is associated with cholesterol levels, which is an established risk factor for atherosclerosis, the underlying cause of coronary artery disease (CAD), a major cause of morbidity and mortality worldwide. However, the exact mechanism and potential genes implicated are still unidentified. To date, Y chromosome-linked long non-coding RNAs (lncRNAs) are poorly characterized and the potential link between these new regulatory RNA molecules and hepatic function in men has not been investigated. Advanced technologies of lncRNA subcellular localization and silencing were used to identify a novel intergenic Y-linked lncRNA, named lnc-KDM5D-4, and investigate its role in fatty liver-associated atherosclerosis. We found that lnc-KDM5D-4 is retained within the nucleus in hepatocytes. Its knockdown leads to changes in genes leading to increased lipid droplets formation in hepatocytes resulting in a downstream effect contributing to the chronic inflammatory process that underpin CAD. Our findings provide the first evidence for the implication of lnc-KDM5D-4 in key processes related to fatty liver and cellular inflammation associated with atherosclerosis and CAD in men.

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Multivessel coronary artery disease, free fatty acids, oxidized LDL and its antibody in myocardial infarction

Cited by 26 publications

References 19 publications

Predicting Diagnostic Gene Biomarkers Associated With Immune Infiltration in Patients With Acute Myocardial Infarction

Predicting Diagnostic Gene Biomarkers Associated With Immune Infiltration in Patients With Acute Myocardial Infarction

IgM anti-malondialdehyde low density lipoprotein antibody levels indicate coronary heart disease and necrotic core characteristics in the Nordic Diltiazem (NORDIL) study and the Integrated Imaging and Biomarker Study 3 (IBIS-3)

A Novel Y-Specific Long Non-Coding RNA Associated with Cellular Lipid Accumulation in HepG2 cells and Atherosclerosis-related Genes

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