Dietary Isoflavones and Coronary Artery Disease—Proposed Molecular Mechanisms of Action

In the article on the example of a clinical case approaches to enhancing antianginal therapy of coronary artery disease were discussed. Arguments were given for prescribing preparations of the second line of antianginal agents (thymetazidine) in the patient with stable angina with high functional class and concomitant hypotonia after a complicated COVID-19. The main mechanisms of action of trimetazidine and results of clinical studies were discussed.

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Integrative genomic analysis identified common regulatory networks underlying the correlation between coronary artery disease and plasma lipid levels

BMC Cardiovascular Disorders ◽

10.1186/s12872-019-01271-9 ◽

2019 ◽

Vol 19 (1) ◽

Author(s):

Liuying Chen ◽

Yinghao Yao ◽

Chaolun Jin ◽

Shen Wu ◽

Qiang Liu ◽

...

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Regulatory Networks ◽

Molecular Mechanisms ◽

Plasma Lipids ◽

Lipid Level ◽

Plasma Lipid ◽

Lipid Levels ◽

Regulatory Relationship ◽

Artery Disease

Abstract Background Coronary artery disease (CAD) and plasma lipid levels are highly correlated, indicating the presence of common pathways between them. Nevertheless, the molecular pathways underlying the pathogenic comorbidities for both traits remain poorly studied. We sought to identify common pathways and key driver genes by performing a comprehensive integrative analysis based on multi-omic datasets. Methods By performing a pathway-based analysis of GWAS summary data, we identified that lipoprotein metabolism process-related pathways were significantly associated with CAD risk. Based on LD score regression analysis of CAD-related SNPs, significant heritability enrichments were observed in the cardiovascular and digestive system, as well as in liver and gastrointestinal tissues, which are the main regulators for lipid level. Results We found there existed significant genetic correlation between CAD and other lipid metabolism related traits (the smallest P value < 1 × 10− 16). A total of 13 genes (e.g., LPA, APOC1, APOE and SLC22A3) was found to be overlapped between CAD and plasma lipid levels. By using the data-driven approach that integrated transcriptome information, we discovered co-expression modules associated prominently with both CAD and plasma lipids. With the detailed topology information on gene-gene regulatory relationship, we illustrated that the identified hub genes played important roles in the pathogenesis of CAD and plasma lipid turbulence. Conclusion Together, we identified the shared molecular mechanisms underlying the correlation between CAD and plasma lipid levels.

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Integration of Gene Expression Profile Data of Human Epicardial Adipose Tissue from Coronary Artery Disease to Verification of Hub Genes and Pathways

BioMed Research International ◽

10.1155/2019/8567306 ◽

2019 ◽

Vol 2019 ◽

pp. 1-9 ◽

Cited By ~ 2

Author(s):

Weitie Wang ◽

Qing Liu ◽

Yong Wang ◽

Hulin Piao ◽

Bo Li ◽

...

Keyword(s):

Coronary Artery Disease ◽

Adipose Tissue ◽

Coronary Artery ◽

Focal Adhesion ◽

Molecular Mechanisms ◽

Epicardial Adipose Tissue ◽

Hub Genes ◽

Qrt Pcr ◽

Ppi Networks ◽

Artery Disease

Background. This study aim to identify the core pathogenic genes and explore the potential molecular mechanisms of human coronary artery disease (CAD). Methodology. Two gene profiles of epicardial adipose tissue from CAD patients including GSE 18612 and GSE 64554 were downloaded and integrated by R software packages. All the coexpression of deferentially expressed genes (DEGs) were picked out and analyzed by DAVID online bioinformatic tools. In addition, the DEGs were totally typed into protein-protein interaction (PPI) networks to get the interaction data among all coexpression genes. Pictures were drawn by cytoscape software with the PPI networks data. CytoHubba were used to predict the hub genes by degree analysis. Finally all the top 10 hub genes and prediction genes in Molecular complex detection were analyzed by Gene ontology and Kyoto encyclopedia of genes and genomes pathway analysis. qRT-PCR were used to identified all the 10 hub genes. Results. The top 10 hub genes calculated by the degree method were AKT1, MYC, EGFR, ACTB, CDC42, IGF1, FGF2, CXCR4, MMP2 and LYN, which relevant with the focal adhesion pathway. Module analysis revealed that the focal adhesion was also acted an important role in CAD, which was consistence with cytoHubba. All the top 10 hub genes were verified by qRT-PCR which presented that AKT1, EGFR, CDC42, FGF2, and MMP2 were significantly decreased in epicardial adipose tissue of CAD samples (p<0.05) and MYC, ACTB, IGF1, CXCR4, and LYN were significantly increased (p<0.05). Conclusions. These candidate genes could be used as potential diagnostic biomarkers and therapeutic targets of CAD.

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Virtual screening and network pharmacology-based synergistic mechanism identification of multiple components contained in Guanxin V against coronary artery disease

BMC Complementary Medicine and Therapies ◽

10.1186/s12906-020-03133-w ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Bo Liang ◽

Xiao-Xiao Zhang ◽

Ning Gu

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Virtual Screening ◽

Molecular Mechanisms ◽

Functional Enrichment ◽

Network Pharmacology ◽

Active Components ◽

Kegg Pathways ◽

Synergistic Mechanism ◽

Artery Disease

Abstract Background Guanxin V (GXV), a traditional Chinese medicine (TCM), has been widely used to treat coronary artery disease (CAD) in clinical practice in China. However, research on the active components and underlying mechanisms of GXV in CAD is still scarce. Methods A virtual screening and network pharmacological approach was utilized for predicting the pharmacological mechanisms of GXV in CAD. The active compounds of GXV based on various TCM-related databases were selected and then the potential targets of these compounds were identified. Then, after the CAD targets were built through nine databases, a PPI network was constructed based on the matching GXV and CAD potential targets, and the hub targets were screened by MCODE. Moreover, Metascape was applied to GO and KEGG functional enrichment. Finally, HPLC fingerprints of GXV were established. Results A total of 119 active components and 121 potential targets shared between CAD and GXV were obtained. The results of functional enrichment indicated that several GO biological processes and KEGG pathways of GXV mostly participated in the therapeutic mechanisms. Furthermore, 7 hub MCODEs of GXV were collected as potential targets, implying the complex effects of GXV-mediated protection against CAD. Six specific chemicals were identified. Conclusion GXV could be employed for CAD through molecular mechanisms, involving complex interactions between multiple compounds and targets, as predicted by virtual screening and network pharmacology. Our study provides a new TCM for the treatment of CAD and deepens the understanding of the molecular mechanisms of GXV against CAD.

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Sarcomeric Gene Variants and Their Role with Left Ventricular Dysfunction in Background of Coronary Artery Disease

Biomolecules ◽

10.3390/biom10030442 ◽

2020 ◽

Vol 10 (3) ◽

pp. 442 ◽

Cited By ~ 2

Author(s):

Surendra Kumar ◽

Vijay Kumar ◽

Jong-Joo Kim

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Left Ventricle ◽

Molecular Mechanisms ◽

Genetic Diagnosis ◽

Left Ventricular ◽

Left Ventricular Ejection ◽

Ventricular Ejection Fraction ◽

Artery Disease ◽

Sarcomeric Genes

Cardiovascular diseases are one of the leading causes of death in developing countries, generally originating as coronary artery disease (CAD) or hypertension. In later stages, many CAD patients develop left ventricle dysfunction (LVD). Left ventricular ejection fraction (LVEF) is the most prevalent prognostic factor in CAD patients. LVD is a complex multifactorial condition in which the left ventricle of the heart becomes functionally impaired. Various genetic studies have correlated LVD with dilated cardiomyopathy (DCM). In recent years, enormous progress has been made in identifying the genetic causes of cardiac diseases, which has further led to a greater understanding of molecular mechanisms underlying each disease. This progress has increased the probability of establishing a specific genetic diagnosis, and thus providing new opportunities for practitioners, patients, and families to utilize this genetic information. A large number of mutations in sarcomeric genes have been discovered in cardiomyopathies. In this review, we will explore the role of the sarcomeric genes in LVD in CAD patients, which is a major cause of cardiac failure and results in heart failure.

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Inflammation-Related Risk Loci in Genome-Wide Association Studies of Coronary Artery Disease

Cells ◽

10.3390/cells10020440 ◽

2021 ◽

Vol 10 (2) ◽

pp. 440

Author(s):

Carina Mauersberger ◽

Heribert Schunkert ◽

Hendrik B. Sager

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Molecular Mechanisms ◽

Association Studies ◽

Genome Wide Association ◽

Considerable Proportion ◽

Genome Wide Association Studies ◽

Genome Wide ◽

Related Risk ◽

Artery Disease

Although the importance of inflammation in atherosclerosis is now well established, the exact molecular processes linking inflammation to the development and course of the disease are not sufficiently understood. In this context, modern genetics—as applied by genome-wide association studies (GWAS)—can serve as a comprehensive and unbiased tool for the screening of potentially involved pathways. Indeed, a considerable proportion of loci discovered by GWAS is assumed to affect inflammatory processes. Despite many well-replicated association findings, however, translating genomic hits to specific molecular mechanisms remains challenging. This review provides an overview of the currently most relevant inflammation-related GWAS findings in coronary artery disease and explores their potential clinical perspectives.

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Association of Pericardiac Adipose Tissue With Coronary Artery Disease

Frontiers in Endocrinology ◽

10.3389/fendo.2021.724859 ◽

2021 ◽

Vol 12 ◽

Author(s):

Mingxuan Li ◽

Lin Qi ◽

Yanglei Li ◽

Shuyi Zhang ◽

Lei Lin ◽

...

Keyword(s):

Coronary Artery Disease ◽

Adipose Tissue ◽

Coronary Artery ◽

Gene Network ◽

Molecular Mechanisms ◽

Inflammatory Cells ◽

Ppi Network ◽

Elective Cardiac Surgery ◽

Pericardial Adipose Tissue ◽

Artery Disease

Background and AimCoronary artery disease (CAD) poses a worldwide health threat. Compelling evidence shows that pericardial adipose tissue (PAT), a brown-like adipose adjacent to the external surface of the pericardium, is associated with CAD. However, the specific molecular mechanisms of PAT in CAD are elusive. This study aims to characterize human PAT and explore its association with CAD.MethodsWe acquired samples of PAT from 31 elective cardiac surgery patients (17 CAD patients and 14 controls). The transcriptome characteristics were assessed in 5 CAD patients and 4 controls via RNA-sequencing. Cluster profile R package, String database, Cytoscape were applied to analyze the potential pathways and PPI-network key to DEGS, whereas the hubgenes were predicted via Metascape, Cytohubba, and MCODE. We use Cibersort, ENCORI, and DGIDB to predict immunoinfiltration, mRNA-miRNA target gene network, and search potential drugs targeting key DEGs. The predictable hubgenes and infiltrating inflammatory cells were validated in 22 patients (12 CAD samples and 10 control samples) through RT-qPCR and immunohistochemistry.ResultsA total of 147 different genes (104 up-regulated genes and 43 down-regulated genes) were identified in CAD patients. These different genes were associated with immunity and inflammatory dysfunction. Cibersort analysis showed monocytes and macrophages were the most common subsets in immune cells, whereas immunohistochemical results revealed there were more macrophages and higher proportion of M1 subtype cells in PAT of CAD patients. The PPI network and module analysis uncovered several crucial genes, defined as candidate genes, including Jun, ATF3, CXCR4, FOSB, CCl4, which were validated through RT-qPCR. The miRNA-mRNA network implicated hsa-miR-185-5p as diagnostic targets and drug-gene network showed colchicine, fenofibrate as potential therapeutic drugs, respectively.ConclusionThis study demonstrates that PAT is mainly associated with the occurrence of CAD following the dysfunction of immune and inflammatory processes. The identified hubgenes, predicted drugs and miRNAs are promising biomarkers and therapeutic targets for CAD.

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Endostatin and angiostatin are increased in diabetic patients with coronary artery disease and associated with impaired coronary collateral formation

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00283.2008 ◽

2009 ◽

Vol 296 (2) ◽

pp. H428-H434 ◽

Cited By ~ 56

Author(s):

Neel R. Sodha ◽

Richard T. Clements ◽

Munir Boodhwani ◽

Shu-Hua Xu ◽

Roger J. Laham ◽

...

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Molecular Mechanisms ◽

Artery Bypass ◽

Cathepsin L ◽

Tissue Inhibitor Of Metalloproteinase ◽

Diabetic Patients ◽

Collagen Xviii ◽

Incomplete Revascularization ◽

Artery Disease

Coronary artery disease (CAD) is the leading cause of mortality in diabetic patients. Because of the diffuse nature of their disease, diabetic patients may be at risk for incomplete revascularization, highlighting a potential role for proangiogenic therapy in this group. This study investigates molecular mechanisms of angiogenesis in diabetic patients. Myocardial tissue was harvested from patients undergoing coronary artery bypass grafting [nondiabetic (ND) 11, type 2 diabetic (DM) 10]. Expression of angiostatin, endostatin, their precursors (plasminogen and collagen XVIII, respectively), enzymes leading to their production [matrix metalloprotease (MMP)-2 and -9, cathepsin L], and an inhibitor of MMPs (tissue inhibitor of metalloproteinase) was assessed with Western blotting. MMP activity was assessed. Coronary collateralization was graded by Rentrop scoring of angiograms. Plasminogen and collagen XVIII expression were similar between groups. Angiostatin expression trended to increase 1.24-fold ( P = 0.07), and endostatin expression increased 2.02-fold in DM patients relative to ND ( P = 0.02). MMP-9 expression was no different between groups, whereas MMP-2 expression decreased 1.8-fold in diabetics ( P = 0.003). MMP-2 and -9 activity decreased 1.33-fold ( P = 0.03) and 1.57-fold ( P = 0.04), respectively, in diabetic patients. Cathepsin L expression was 1.38-fold higher in diabetic patients ( P = 0.02). Coronary collateralization scores were ND 2.1 ± 0.37 vs. DM 1.0 ± 0.4 ( P = 0.05). Myocardial endostatin expression correlated strongly with the percentage of hemoglobin A1c ( r = 0.742, P = 0.0001). Myocardial expression of angiostatin and endostatin demonstrated significant negative linear correlations with coronary collateralization (angiostatin r = −0.531, P = 0.035, endostatin r = −0.794, P = 0.0002). Diabetic patients with CAD exhibit increased levels of the antiangiogenic proteins angiostatin and endostatin and differential regulation of the enzymes governing their production relative to ND patients. Myocardial levels of these proteins show significant correlation to coronary collateralization. These findings offer potential new therapeutic targets for enhancing proangiogenic therapy and insight into the angiogenic impairments seen in diabetes.

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Opium may affect coronary artery disease by inducing inflammation but not through the expression of CD9, CD36, and CD68

Journal of Investigative Medicine ◽

10.1136/jim-2021-001935 ◽

2021 ◽

pp. jim-2021-001935

Author(s):

Mohammad Amin Momeni-Moghaddam ◽

Gholamreza Asadikaram ◽

Mohammad Masoumi ◽

Erfan Sadeghi ◽

Hamed Akbari ◽

...

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Messenger Rna ◽

Molecular Mechanisms ◽

Control Group ◽

Mrna Levels ◽

Tnf Α ◽

Opium Addiction ◽

Ifn Γ ◽

Artery Disease

The molecular mechanisms of opium with regard to coronary artery disease (CAD) have not yet been determined. The aim of the present study was to evaluate the effect of opium on the expression of scavenger receptors including CD36, CD68, and CD9 tetraspanin in monocytes and the plasma levels of tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-γ), malondialdehyde (MDA), and nitric oxide metabolites (NOx) in patients with CAD with and without opium addiction. This case–control study was conducted in three groups: (1) opium-addicted patients with CAD (CAD+OA, n=30); (2) patients with CAD with no opium addiction (CAD, n=30); and (3) individuals without CAD and opium addiction as the control group (Ctrl, n=17). Protein and messenger RNA (mRNA) levels of CD9, CD36, and CD68 were evaluated by flow cytometry and reverse transcription-quantitative PCR methods, respectively. Consumption of atorvastatin, aspirin, and glyceryl trinitrate was found to be higher in the CAD groups compared with the control group. The plasma level of TNF-α was significantly higher in the CAD+OA group than in the CAD and Ctrl groups (p=0.001 and p=0.005, respectively). MDA levels significantly increased in the CAD and CAD+OA groups in comparison with the Ctrl group (p=0.010 and p=0.002, respectively). No significant differences were found in CD9, CD36, CD68, IFN-γ, and NOx between the three groups. The findings demonstrated that opium did not have a significant effect on the expression of CD36, CD68, and CD9 at the gene and protein levels, but it might be involved in the development of CAD by inducing inflammation through other mechanisms.

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Effects of exercise training on coronary collateralization and control of collateral resistance

Journal of Applied Physiology ◽

10.1152/japplphysiol.00338.2011 ◽

2011 ◽

Vol 111 (2) ◽

pp. 587-598 ◽

Cited By ~ 27

Author(s):

Cristine L. Heaps ◽

Janet L. Parker

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Exercise Training ◽

Collateral Circulation ◽

Molecular Mechanisms ◽

Contractile Function ◽

Ischemic Myocardium ◽

Protective Mechanism ◽

Therapeutic Benefits ◽

Artery Disease

Coronary collateral vessels serve as a natural protective mechanism to provide coronary flow to ischemic myocardium secondary to critical coronary artery stenosis. The innate collateral circulation of the normal human heart is typically minimal and considerable variability occurs in extent of collateralization in coronary artery disease patients. A well-developed collateral circulation has been documented to exert protective effects upon myocardial perfusion, contractile function, infarct size, and electrocardiographic abnormalities. Thus therapeutic augmentation of collateral vessel development and/or functional adaptations in collateral and collateral-dependent arteries to reduce resistance into the ischemic myocardium represent a desirable goal in the management of coronary artery disease. Tremendous evidence has provided documentation for the therapeutic benefits of exercise training programs in patients with coronary artery disease (and collateralization); mechanisms that underlie these benefits are numerous and multifaceted, and currently under investigation in multiple laboratories worldwide. The role of enhanced collateralization as a major beneficial contributor has not been fully resolved. This topical review highlights literature that examines the effects of exercise training on collateralization in the diseased heart, as well as effects of exercise training on vascular endothelial and smooth muscle control of regional coronary tone in the collateralized heart. Future directions for research in this area involve further delineation of cellular/molecular mechanisms involved in effects of exercise training on collateralized myocardium, as well as development of novel therapies based on emerging concepts regarding exercise training and coronary artery disease.

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