Progression Of Coronary Heart Disease Research Articles

Novel Diagnostic Biomarkers Related to Necroptosis and Immune Infiltration in Coronary Heart Disease.

Necroptosis, a monitored form of inflammatory cell death, contributes to coronary heart disease (CHD) progression. This study examined the potential of using necroptosis genes as diagnostic markers for CHD and sought to elucidate the underlying roles. Through bioinformatic analysis of GSE20680 and GSE20681, we first identified the differentially expressed genes (DEGs) related to necroptosis in CHD. Hub genes were identified using least absolute shrinkage and selection operator (LASSO) regression and random forest analysis after studying immune infiltration and transcription factor-miRNA interaction networks according to the DEGs. Quantitative polymerase chain reaction and immunohistochemistry were used to further investigate hub gene expression in vivo, for which a diagnostic model was constructed and the predictive efficacy was validated. Finally, the CHD group was categorized into high- and low-score groups in accordance with the single-sample gene set enrichment analysis (ssGSEA) score of the necroptosis genes. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, GSEA, and further immune infiltration analyses were performed on the two groups to explore the possible roles of hub genes. Based on the results of the LASSO regression and random forest analyses, four genes were used to construct a diagnostic model to establish a nomogram. Additionally, an extensive analysis of all seventeen necroptosis genes revealed notable distinctions in expression between high-risk and low-risk groups. Evaluation of immune infiltration revealed that neutrophils, monocytes, B cells, and activated dendritic cells were highly distributed in the peripheral blood of patients with CHD. Specifically, the high CHD score group exhibited greater neutrophil and monocyte infiltration. Conversely, the high-score group showed lower infiltration of M0 and M2 macrophages, CD8+ T, plasma, and resting mast cells. TLR3, MLKL, HMGB1, and NDRG2 may be prospective biomarkers for CHD diagnosis. These findings offer plausible explanations for the role of necroptosis in CHD progression through immune infiltration and inflammatory response.

Plasma proteome association with coronary heart disease and carotid intima media thickness: results from the KORA F4 study

Background and aimsAtherosclerosis is the main cause of stroke and coronary heart disease (CHD), both leading mortality causes worldwide. Proteomics, as a high-throughput method, could provide helpful insights into the pathological mechanisms underlying atherosclerosis. In this study, we characterized the associations of plasma protein levels with CHD and with carotid intima-media thickness (CIMT), as a surrogate measure of atherosclerosis.MethodsThe discovery phase included 1000 participants from the KORA F4 study, whose plasma protein levels were quantified using the aptamer-based SOMAscan proteomics platform. We evaluated the associations of plasma protein levels with CHD using logistic regression, and with CIMT using linear regression. For both outcomes we applied two models: an age-sex adjusted model, and a model additionally adjusted for body mass index, smoking status, physical activity, diabetes status, hypertension status, low density lipoprotein, high density lipoprotein, and triglyceride levels (fully-adjusted model). The replication phase included a matched case-control sample from the independent KORA F3 study, using ELISA-based measurements of galectin-4. Pathway analysis was performed with nominally associated proteins (p-value < 0.05) from the fully-adjusted model.ResultsIn the KORA F4 sample, after Bonferroni correction, we found CHD to be associated with five proteins using the age-sex adjusted model: galectin-4 (LGALS4), renin (REN), cathepsin H (CTSH), and coagulation factors X and Xa (F10). The fully-adjusted model yielded only the positive association of galectin-4 (OR = 1.58, 95% CI = 1.30–1.93), which was successfully replicated in the KORA F3 sample (OR = 1.40, 95% CI = 1.09–1.88). For CIMT, we found four proteins to be associated using the age-sex adjusted model namely: cytoplasmic protein NCK1 (NCK1), insulin-like growth factor-binding protein 2 (IGFBP2), growth hormone receptor (GHR), and GDNF family receptor alpha-1 (GFRA1). After assessing the fully-adjusted model, only NCK1 remained significant (β = 0.017, p-value = 1.39e-06). Upstream regulators of galectin-4 and NCK1 identified from pathway analysis were predicted to be involved in inflammation pathways.ConclusionsOur proteome-wide association study identified galectin-4 to be associated with CHD and NCK1 to be associated with CIMT. Inflammatory pathways underlying the identified associations highlight the importance of inflammation in the development and progression of CHD.

Molecular mechanism of Danxiong Tongmai Granules in treatment of coronary heart disease.

Danxiong Tongmai Granules (DXTMG) are widely utilized in treating coronary heart disease (CHD) in China. This study aims to explore the molecular mechanisms underlying the therapeutic effects of DXTMG on CHD by employing a network pharmacology approach, complemented with experimental validation. Traditional Chinese Medicine (TCM) compounds and targets were identified via searches in the BATMAN-TCM database, and the GeneCards database was used to obtain the main target genes involved in CHD. We combined disease targets with the drug targets to identify common targets. The "TCM-compound-target" network was plotted using Cytoscape 3.7.2 software and a protein-protein interaction (PPI) network was constructed using the STRING database from which core targets were obtained. Gene ontology (GO) function analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed for common drug-disease targets using R Version 4.0.4 (64 bit) software. Molecular docking of core protein-small molecule ligand interaction was modeled using AutoDock software. A molecular dynamics simulation was conducted on the optimal protein-small molecule complex identified through molecular docking, using Amber18 software. The rat model for myocardial ischemia was established through pre-gavage administration of DXTMG, followed by dorsal hypodermic injection of isoprenaline. Myocardial tissues from the rats were analyzed using hematoxylin and eosin (HE) staining and Masson's trichrome staining. Relevant targets were validated by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry. 162 potential targets of DXTMG involved in CHD were identified. These included INS, ALB, IL-6 and TNF according to PPI network studies. GO enrichment analysis identified a total of 3365 GO pathways, including 3049 biological process pathways (BP) concerned with the heart and circulatory system; 109 cellular component (CC) pathways, including cation channels and membrane rafts and 207 molecular function (MF) pathways related to receptor ligands and activators. KEGG analysis revealed a total of 137 pathways (P < 0.05), including those related to AGE-RAGE signaling associated with diabetic complications, fluid shear stress and atherosclerosis. The results of molecular docking and molecular dynamics simulations demonstrated the robust binding affinity between the compounds and target proteins. Animal experiment findings indicated that, compared with the model group, the DXTMG group effectively ameliorated inflammation and fibrosis in rat myocardial tissues, reduced LDH, cTn-I, and MDA levels (P < 0.05, P < 0.01), elevated SOD and GSH-PX levels (P < 0.05), and reduced the percentage of positive area for IL-6 and TNF-α (P < 0.05). This study preliminarily suggests that DXTMG can modulate oxidative stress, inflammation response, and cardiomyocyte regulation, thereby mitigating the onset and progression of CHD.

The impact of serum BNP on retinal perfusion assessed by an AI-based denoising optical coherence tomography angiography in CHD patients

BackgroundTo investigate the correlation between retinal vessel density (VD) parameters with serum B-type natriuretic peptide (BNP) in patients with coronary heart disease (CHD) using novel optical coherence tomography angiography (OCTA) denoising images based on artificial intelligence (AI). MethodsOCTA images of the optic nerve and macular area were obtained using a Canon-HS100 OCT device in 176 patients with CHD. Baseline information and blood test results were recorded. ResultsRetinal VD parameters of the macular and optic nerves on OCTA were significantly decreased in patients with CHD after denoising. Retinal VD of the superficial capillary plexus (SCP), deep capillary plexus (DCP) and radial peripapillary capillary (RPC) was strongly correlated with serum BNP levels in patients with CHD. Significant differences were noted in retinal thickness and retinal VD (SCP, DCP and RPC) between the increased BNP and normal BNP groups in patients with CHD. ConclusionDeep learning denoising can remove background noise and smooth rough vessel surfaces. SCP,DCP and RPC may be potential clinical markers of cardiac function in patients with CHD. Denoising shows great potential for improving the sensitivity of OCTA images as a biomarker for CHD progression.

Effects of Ninjurin 2 polymorphisms on susceptibility to coronary heart disease

ABSTRACT Objective The aim of this study was to explore the effects of Ninjurin 2 (NINJ2) polymorphisms on susceptibility to coronary heart disease (CHD). Methods We conducted a case-control study with 499 CHD cases and 505 age and gender-matched controls. Five single nucleotide polymorphisms (SNPs) in NINJ2 (rs118050317, rs75750647, rs7307242, rs10849390, and rs11610368) were genotyped by the Agena MassARRAY platform. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression analysis to assess the association of NINJ2 polymorphisms and CHD risk-adjusted for age and gender. What’s more, risk genes and molecular functions were screened via protein-protein interaction (PPI) network and functional enrichment analysis. Results Rs118050317 in NINJ2 significantly increased CHD risk in people aged more than 60 years and women. Rs118050317 and rs7307242 had strong relationships with hypertension risk in CHD patients. Additionally, rs75750647 exceedingly raised diabetes risk in cases under multiple models, whereas rs10849390 could protect CHD patients from diabetes in allele, homozygote, and additive models. We also observed two blocks in NINJ2. Further interaction network and enrichment analysis showed that NINJ2 played a greater role in the pathogenesis and progression of CHD. Conclusion Our results suggest that NINJ2 polymorphisms are associated with CHD risk.

Taking appreciation to heart: appreciation at work and cardiovascular risk in male employees.

While perceived appreciation at work has been associated with self-reported health and wellbeing, studies considering biological health markers are lacking. In this study, we investigated whether appreciation at work would relate to coronary heart disease (CHD) risk as well as the specificity of this proposed association. Our study comprised a total of 103 male participants, including apparently healthy, medication-free, non-smoking men in the normotensive to hypertensive range (n = 70) as well as medicated hypertensive and CHD patients (n = 33). CHD risk was assessed by blood pressure [mean arterial pressure (MAP)], the diabetes marker glycated hemoglobin A1c (HbA1c), blood lipids [total cholesterol (TC)/high-density lipoprotein-cholesterol (HDL-C) ratio], coagulation activity (D-dimer and fibrinogen), and inflammation [interleukin (IL)-6, tumor necrosis factor-alpha (TNF-α), and C-reactive protein (CRP)]. Perceived appreciation at work, as well as potentially confounding psychological factors (social support, self-esteem, and work strain due to a lack of appreciation), were measured by self-report questionnaires. We found higher appreciation at work to relate to lower overall composite CHD risk (p's ≤ 0.011) and, in particular, to lower MAP (p's ≤ 0.007) and lower blood lipids (p's ≤ 0.031) in medication-free participants as well as all participants. This overall association was independent of confounding factors, including related psychological factors (p's ≤ 0.049). Our findings indicate that appreciation at work might be an independent health-promoting resource in terms of CHD risk. Implications include that encouraging appreciation at work may help reduce the development and progression of CHD.

Depression and coronary heart disease: mechanisms, interventions, and treatments.

Coronary heart disease (CHD), a cardiovascular condition that poses a significant threat to human health and life, has imposed a substantial economic burden on the world. However, in contrast to conventional risk factors, depression emerges as a novel and independent risk factor for CHD. This condition impacts the onset and progression of CHD and elevates the risk of adverse cardiovascular prognostic events in those already affected by CHD. As a result, depression has garnered increasing global attention. Despite this growing awareness, the specific mechanisms through which depression contributes to the development of CHD remain unclear. Existing research suggests that depression primarily influences the inflammatory response, Hypothalamic-pituitary-adrenocortical axis (HPA) and Autonomic Nervous System (ANS) dysfunction, platelet activation, endothelial dysfunction, lipid metabolism disorders, and genetics, all of which play pivotal roles in CHD development. Furthermore, the effectiveness and safety of antidepressant treatment in CHD patients with comorbid depression and its potential impact on the prognosis of CHD patients have become subjects of controversy. Further investigation is warranted to address these unresolved questions.

Role of angiotensin II and neuroendocrine factors in immunological regulation in patients with coronary heart disease: prospective cross-sectional study

BACKGROUND: Among chronic noncommunicable diseases, cardiovascular diseases, particularly coronary heart disease (CHD), are the leading cause of death. The rennin-angiotensin-aldosterone system plays an important role in CHD development and progression; however, its role in the regulation of immunoneuroendocrine interactions requires further analysis.&#x0D; OBJECTIVE: To study the relationship between angiotensin II (AT II) and molecular regulators of the activity of whole blood mononuclear cells (MNCs) in patients with angina pectoris.&#x0D; MATERIALS AND METHODS: This cross-sectional study enrolled 65 patients with exertional angina aged 45–67 years, including 19 apparently healthy individuals. The levels of interleukins (ILs), transforming growth factor-β1 (TGF-β1), prostaglandin E2 (PG E2), serotonin, thyroid-stimulating hormone (TSH), and AT II in the blood serum were determined. In MNCs, the concentrations of protein kinases FAK, JNK, p38, and ERK, signal transducers, and activators of transcription (STAT 3, 5A, and 6) were determined.&#x0D; RESULTS: In patients with coronary artery disease, the production of TGF-β1 increased by 7.2% (p=0.00001), AT II by 136.9% (p=0.0001), serotonin by 129.0% (p=0.00001), IL-18 by 92.5% (p=0.00001), TSH by 51.7% (p=0.0012), ERK protein kinase content by 86.4% (p=0.0001), JNK by 56.8% (p=0.0001), and FAK by 55.3% (p=0.00002). The levels of IL-15 also decreased by 38.1% (p=0.0001), PG E2 by 39.5% (p=0.0001), and STAT3 by 52.5% (p=0.0001).&#x0D; CONCLUSION: The nature of the identified relationships among the analyzed factors allows us to consider AT II as a factor that ensures adaptive coupling of immune and neuroendocrine regulatory mechanisms in patients with coronary artery disease, contributing to a change in the balance between macrophages and T-helper types 1 and 2.

The value of serum lipoprotein-associated phospholipase A2, ischemia-modified albumin, and cystatin C in predicting coronary heart disease risk: a single center retrospective cohort study.

This study aims to explore the value of serum lipoprotein-associated phospholipase A2 (Lp-PLA2), ischemia-modified albumin (IMA), and cystatin C (Cys-C) in predicting the risk of coronary heart disease (CHD). Clinical data from 104 CHD patients admitted to our hospital from January 2020 to December 2022 were analyzed. Of them, 31 patients had stable angina (Group-S), 36 patients were diagnosed with unstable angina (Group-U), and 37 patients had acute myocardial infarction (Group-A). Additionally, clinical data from 35 healthy individuals undergoing physical examination during the same time period were selected as the control group. Levels of blood lipid indicators and serum Lp-PLA2, IMA, and Cys-C levels were compared between the groups. The rates of diabetes, hypertension, and smoking in Group-S, Group-U, and Group-A were significantly higher than those in the control group (p<0.05). Levels of Lp-PLA2, IMA, and Cys-C in Group-S, Group-U, and Group-A were significantly higher than those in the control group (p<0.05). Levels of Lp-PLA2, IMA, and Cys-C in Group-U and Group-A were significantly higher than those in Group-S, and Group-A had the highest value of these indexes (p<0.05). Multivariate logistic regression analysis showed that Lp-PLA2, Cys-C, and IMA were important risk factors for the onset of CHD (p<0.05). Receiver operating characteristic (ROC) curve analysis showed that the area under the curve (AUC) of Lp-PLA2, IMA, and Cys-C predicting the occurrence of CHD was 0.775, 0.835, and 0.735, respectively. The combined prediction of the three factors has an AUC of 0.920, which is higher than the individual prediction. Lp-PLA2, IMA, and Cys-C are closely related to the onset and progression of CHD. These indicators, therefore, can be used in clinical practice to predict and evaluate CHD.

Sirtuin1, not NAMPT, possesses anti-inflammatory effects in epicardial, pericardial and subcutaneous adipose tissue in patients with CHD

BackgroundInflammation in cardiac adipose tissue (AT) is associated with atherosclerosis. We investigated whether the epicardial-, pericardial and pre-sternal subcutaneous AT (EAT, PAT and SAT) expression of Sirtuin1 (SIRT1) and nicotinamide phosphoribosyl transferase (NAMPT) are involved in the inflammatory process in coronary heart disease (CHD), and potentially associated to nod-like receptor family pyrin domain containing 3 (NLRP3) inflammasome-related markers, macrophage polarization markers, cell markers and the cardiometabolic profile.MethodsIn this cohort study performed between 2016 and 2018, EAT, PAT and SAT biopsies were retrieved from 52 CHD patients (77% men, median age 67) undergoing open-chest coronary artery bypass grafting (CABG), and 22 patients (50% men, median age 69) undergoing aortic valve replacement serving as controls. AT samples were snap-frozen at – 80 °C until RNA extraction and AT expression of actual markers, relatively quantified by PCR. Circulating SIRT1 and NAMPT were measured with Enzyme-linked immunosorbent assays (ELISAs). Non-parametric statistical tests were mainly used, including Friedman’s test coupled to Wilcoxon signed-rank test and Spearman Correlation.ResultsSIRT1 and NAMPT levels were similar in CHD and controls. In CHD, SIRT1 and NAMPT were inter-correlated in all AT compartments (r = 0.37–0.56, p < 0.01, all), and differently expressed between compartments, with the highest expression in SAT, significantly different from EAT (p < 0.01, both). Circulating SIRT1 and NAMPT levels were inversely associated (r = − 0.32, p = 0.024). In EAT and SAT, SIRT1 expression was inversely associated with IL-18 (r = − 0.43 and r = − 0.38, p < 0.01, both), whereas NAMPT expression was positively associated with the NLRP3 inflammasome-related markers in all compartments (r = 0.37–0.55, p < 0.01, all). While SIRT1 and NAMPT correlated to nitric oxide synthase 2 (NOS2), especially in SAT (r = 0.50–0.52, p ≤ 0.01, both), SIRT1 expression was related to endothelial cells, and NAMPT to macrophages. SIRT1 levels were correlated to weight and waist (r = 0.32 and r = 0.38, p < 0.03, both) and inversely to triglycerides and glycated haemoglobin (HbA1c) (r = − 0.33–− 0.37, p < 0.03, all), the latter positively correlated to NAMPT concentration (r = 0.39, p = 0.010).ConclusionThe study indicates that targeting SIRT1, with its anti-inflammatory properties, may be a novel anti-inflammatory strategy in preventing atherosclerosis and CHD progression. NAMPT may be an early player in AT inflammation, mediating/reflecting a pro-inflammatory state.Trial Registration: Registration: Clinicaltrials.gov ID: NCT02760914, registered the 5th of February 2016, http://clinicaltrials.gov/NCT02760914Graphical

Electrocardiogram Analysis of Wistar Rats Induced by Hyperlipidemia using Wireless Mice Electrocardiogram (Wim ECG) in Coronary Heart Disease Study

Coronary heart disease (CHD) is a life-threatening disease caused by obstruction of the coronary arteries that interferes with blood flow known as atherosclerosis. Hyperlipidemia, a risk factor of atherosclerosis, is characterized by excessive concentrations of total cholesterol, LDL, and triglycerides with low concentrations of HDL. A high-fat diet (HFD) contributes to the progression of atherosclerosis, CHD, and other cardiovascular diseases. This study aims to measure electrocardiography (ECG) waves of hyperlipidemia-induced rats. Twenty rats were fed different diets for eight weeks, i.e., the control group (normal diet) and the HFD group (high-fat diet). Their ECG was recorded using a Wireless Mice Electrocardiogram (WIM ECG) for 5-10 min. After eight weeks, the HFD group showed a significantly higher lipid profile concentration (cholesterol: 179.03 mg/dL, triglyceride: 149.11 mg/dL, LDL: 123 mg/dL, HDL: 29.15 mg/dL) than the control. This hyperlipidemic condition causes a significant change in some characteristics of the ECG wave. At week 8, the characteristic ECG wave duration for the HFD groups was RR intervals (176.5 ms), QT intervals (123.5 ms), T waves (33.6 ms), P wave (27.4 ms), QRS interval (64.9 ms), ST-segment (23.7 ms), and heart rate (334 bpm). This study concludes that long-period HFD feeding in rats leads to hyperlipidemia and causes changes in the characteristics of ECG waves.

Effects of Chinese Medicine on Pyroptosis in Coronary Heart Disease.

Pyroptosis, an apoptotic pathway for pro-inflammatory cells, has attracted attention from researchers because of its role in the development of cardiac inflammation reactions. Chinese medicine (CM) has been given more and more attention during the pursuit of a treatment for coronary heart disease (CHD). Evidence suggests that myocardial cell pyroptosis affects the progression of CHD. Pyroptosis pathways include the canonical pyroptosis pathway mediated by the caspase-1 inflammasome and the non-canonical pyroptosis pathway induced by cytoplasmic lipopolysaccharide-activated caspase-4/5/11. The frequently studied compounds that regulate pyroptosis in CHD include astragaloside IV (AS-IV), tanshinone IIA, aucubin, cinnamaldehyde (CD), ginsenoside Rb1, paeoniflorin, apigenin, berberine (BBR), ruscogenin (Rus), and total glucosides of paeonia (TGP). The patent drugs of CM that regulate pyroptosis in CHD include the Qishen granule (QSG), the Simiao Yong'an decoction (SMYAD), the Buyang Huanwu decoction (BYHWD), and the Shexiang Baoxin pill (SBP). Therefore, this paper reviews the pathogenesis of pyroptosis, the role of pyroptosis in CHD, and the potential therapeutic roles of CMs and their active ingredients targeting cell pyroptosis in the development of CHD.

Stress Levels Among Men and Women with Coronary Heart Disease. Is there a Difference?

Coronary Heart Disease (CHD) is one of the non-communicable diseases with a very high mortality rate. CHD can occur in both men and women. CHD is usually followed by psychological reactions such as stress, and stress may contribute to progression of CHD. This study aims to determine the difference between stress levels in men and women with CHD. This research used comparative quantitative methods that used a questionnaire from Kessler Psychological Distress K10. Enrolled 95 samples by random sampling. The results of this study showed that there is no difference in stress levels among men and women with CHD (p=0.083, 0.05). Both men and women with CAD have experienced stress, but there is no significant difference between men and women.

Stilbene-based derivatives as potential inhibitors of trimethylamine (TMA)-lyase affect gut microbiota in coronary heart disease.

Coronary heart disease (CHD) is defined by atherosclerosis, which may result in stenosis or blockage of the arterial cavity, leading to ischemic cardiac diseases such as angina and myocardial infarction (MI). Accumulating evidence indicates that the gut microbiota play a critical role in the initiation and progression of CHD. The gut microbial metabolite trimethylamine N-oxide (TMAO) is intimately linked to the pathophysiology of CHD. The hepatic flavin-containing monooxygenases (FMOs) convert trimethylamine (TMA) to TMAO. As a result, it is critical to prevent TMA generation. Stilbenes could reduce cardiovascular disease mortality. Twelve stilbenes with inhibitory activity against TMA-lyase were compiled and evaluated in this study. Docking results showed Resveratroloside had the highest Vina score, indicating that it was the most active and might be employed as a lead molecule for further structural modification.

From Iron Metabolism to Ferroptosis: Pathologic Changes in Coronary Heart Disease.

Coronary heart disease (CHD) is closely related to oxidative stress and inflammatory response and is the most common cardiovascular disease (CVD). Iron is an essential mineral that participates in many physiological and biochemical reactions in the human body. Meanwhile, on the negative side, iron has an active redox capacity, which leads to the accumulation of reactive oxygen species (ROS) and lipid peroxidation. There is growing evidence that disordered iron metabolism is involved in CHD's pathological progression. And the result of disordered iron metabolism is associated with iron overload-induced programmed cell death, often called ferroptosis. That features iron-dependent lipid peroxidation. Ferroptosis may play a crucial role in the development of CHD, and targeting ferroptosis may be a promising option for treating CHD. Here, we review the mechanisms of iron metabolism in cardiomyocytes (CMs) and explain the correlation between iron metabolism and ferroptosis. Meanwhile, we highlight the specific roles of iron metabolism and ferroptosis in the main pathological progression of CHD.

Virtual screening analysis of natural flavonoids as trimethylamine (TMA)-lyase inhibitors for coronary heart disease.

Coronary heart disease (CHD) is defined by atherosclerosis, which can result in stenosis or blockage of the arterial cavity, leading to ischemic cardiac diseases such as angina and myocardial infarction. Accumulating evidence indicates that the gut microbiota plays a vital role in the beginning and progression of CHD. The gut microbial metabolite, trimethylamine-N-oxide (TMAO), is intimately linked to the pathophysiology of CHD. TMAO is formed when trimethylamine (TMA) is converted by flavin-containing monooxygenases in the hepatocytes. Therefore, inhibition of TMA production is essential to reduce TMAO levels. Flavonoids may reduce the risk of death from cardiovascular disease. In this article, we reviewed and evaluated twenty-two flavonoids for the therapy of CHD based on their inhibition of TMA-lyase by molecular docking. Docking results revealed that baicalein, fisetin, acacetin, and myricetin in flavonoid aglycones, and baicalin, naringin, and hesperidin in flavonoid glycosides had a good binding effect with TMA-lyase. This indicates that these chemicals were the most active and could be used as lead compounds for structural modification in the future. PRACTICAL APPLICATIONS: Flavonoids are a large class of polyphenolic compounds found in fruits, vegetables, flowers, tea, and herbal medicines, which are inexorably metabolized and transformed into bioactive metabolites by α-rhamnosidase, β-glucuronidase, β-glucosidase, and nitroreductase produced by the gut microbiota, which plays a beneficial role in the prevention and treatment of cardiovascular diseases. Because flavonoids protect the cardiovascular system and regulate the gut microbiota, and the gut microbiota is directly connected to TMAO, thus, reducing TMAO levels involves blocking the transition of TMA to TMAO, which may be performed by reducing TMA synthesis. Molecular docking results found that baicalein, fisetin, acacetin, and myricetin in flavonoid aglycones, and baicalin, naringin, and hesperidin in flavonoid glycosides had good binding effects on TMA-lyase, which were the most active and could be used as lead compounds for structural modification.

Rehabilitation effects of circuit resistance training in coronary heart diseasepatients: A systematic review and meta-analysis.

Background and HypothesisThe rehabilitation effect of circuit resistance training in coronary heart disease (CHD) patients remains unclear. We perform this review to examine the rehabilitation effect of circuit resistance training in CHD patients and to provide a basis for the formulation of reasonable individual exercise prescriptions for CHD patients.MethodsRandomized controlled trials (RCTs) were searched on PubMed, Web of Science, The Cochrane Library, Embase, Clinical Trials, and CNKI. About 1232 studies were identified. Nine RCTs were finally used for the present meta‐analysis to determine the rehabilitation effect of circuit resistance training in CHD patients, compared to aerobic training. Individuals enrolled for the studies were at a mean age of 60.5 years old and were all CHD patients. Following the PRISMA guidelines, we extracted basic information about the study and patient characteristics, as well as measurements (e.g., the peak oxygen uptake, the body mass index [BMI], the body fat percentage, the systolic blood pressure, the total cholesterol, and triglycerides). Subsequently, this meta‐analysis determined the overall effect by using standardized mean difference (SMD) and 95% confidence interval (CI).ResultsCompared with aerobic training, circuit resistance training significantly decrease the BMI and the body fat percentage.ConclusionsAs suggested from the present meta‐analysis of RCTs, circuit resistance training is effective in improving the BMI and the body fat percentage in CHD patients and may help delay the progression of CHD. CRT has the advantage of lower load in most cases with a similar effect.

Analysis of Risk Factors of Coronary Heart Disease and Its Correlation with Inflammatory Factors in Patients with Type 2 Diabetes Mellitus.

In this paper, we propose a new method to analyze the risk factors of coronary heart disease (CHD) and their correlation with inflammatory factors in patients with type 2 diabetes mellitus (T2DM). To verify and implement this idea, we have selected a total of 165 patients with T2DM treated in our hospital from March 2019 to October 2021 that were divided into CHD group (n = 72) and non-CHD group (n = 93) according to the results of coronary angiography. Patients with CHD were divided into three groups according to SYNTAX score: low-risk group, medium-risk group, and high-risk group. The clinical data of all patients were collected. Univariate and multivariate analyses were used to screen the risk factors of CHD in patients with T2DM. The related inflammatory factors such as C-reactive protein (CRP), interleukin-6 (IL-6), and water-soluble CD40 ligand (sCD40L) were detected in all patients. Pearson's linear correlation analysis was used to analyze the correlation between the expression levels of CRP, IL-6, and sCD40L and CHD in patients with T2DM. The receiver working curve (ROC) was used to evaluate the efficacy of IL-6, CRP, and sCD40L in predicting high risk of CHD in patients with T2DM. Multivariate analysis showed that age and course of T2DM, FFA, UA, and Hcy were risk factors for CHD in patients with T2DM. The serum levels of IL-6, CRP, and sCD40L in patients with CHD were significantly higher than those in patients without CHD. According to SYNTAX score, 72 patients with CHD were divided into low-risk group (n = 36), medium-risk group (n = 26), and high-risk group (n = 10). Compared with the low-risk group, the expression levels of serum IL-6 CRP and sCD40L in the middle-risk group and high-risk group were significantly higher than those in the low-risk group. The expression levels of IL-6 CRP and sCD40L in the high-risk group were also significantly higher than those in the medium-risk group. There is a positive correlation between syntactic score and IL-6 expression in patients with T2DM complicated with coronary heart disease (r = 0.778, P < 0.001), with the expression of CRP (r = 0.756, P < 0.001) and with the expression of sCD40L (r = 0.748, P < 0.001). Advanced age, long course of T2DM, elevated levels of FFA, UA, and Hcy are all risk factors of CHD in patients with type 2 diabetes. T2DM patients with the above risk factors should be vigilant and pay attention to monitoring the related indexes of coronary heart disease to avoid the occurrence of serious cardiovascular disease. CRP, IL-6, and sCD40L are involved in the progression of CHD in patients with T2DM. The more severe CHD is, the higher the expression of IL-6, CRP, and sCD40L in serum.

A Network Pharmacology Study to Explore the Underlying Mechanism of Safflower (Carthamus tinctorius L.) in the Treatment of Coronary Heart Disease.

Safflower has long been used to treat coronary heart disease (CHD). However, the underlying mechanism remains unclear. The goal of this study was to predict the therapeutic effect of safflower against CHD using a network pharmacology and to explore the underlying pharmacological mechanisms. Firstly, we obtained relative compounds of safflower based on the TCMSP database. The TCMSP and PubChem databases were used to predict targets of these active compounds. Then, we built CHD-related targets by the DisGeNET database. The protein-protein interaction (PPI) network graph of overlapping genes was obtained after supplying the common targets of safflower and CHD into the STRING database. The PPI network was then used to determine the top ten most significant hub genes. Furthermore, the DAVID database was utilized for the enrichment analysis on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). To validate these results, a cell model of CHD was established in EAhy926 cells using oxidized low-density lipoprotein (ox-LDL). Safflower was determined to have 189 active compounds. The TCMSP and PubChem databases were used to predict 573 targets of these active compounds. The DisGeNET database was used to identify 1576 genes involved in the progression of CHD. The top ten hub genes were ALB, IL6, IL1B, VEGFA, STAT3, MMP9, TLR4, CCL2, CXCL8, and IL10. GO functional enrichment analysis yielded 92 entries for biological process (BP), 47 entries for cellular component (CC), 31 entries for molecular function (MF), and 20 signaling pathways, which were obtained from KEGG pathway enrichment screening. Based on these findings, the FoxO signaling pathway is critical in the treatment of CHD by safflower. The in vitro results showed that safflower had an ameliorating effect on ox-LDL-induced apoptosis and mitochondrial membrane potential. The western blot results showed that safflower decreased Bax expression and acetylation of FoxO1 proteins while increasing the expression of Bcl-2 and SIRT1 proteins. Safflower can be used in multiple pathways during CHD treatment and can exert anti-apoptotic effects by regulating the expression of Bax, Bcl-2, and SIRT1/FoxO1 signaling pathway-related proteins.

ANALYSIS OF CLINICAL AND FUNCTIONAL INDICES OF CARDIOVASCULAR SYSTEM IN POST-COVID-19 EMERGENCY WORKERS OF THE CHORNOBYL ACCIDENT.

to determine which changes of cardiovascular system clinical, and structural, and functional state in emergency workers (EW) of the accident at the Chornobyl nuclear power plant (CNNP) can be associated with COVID-19 they suffered from and not with the natural progression of coronary heart disease (CHD). The study included 16 male EW who fell ill with mild and medium-severe COVID-19 (EWC group) in 2020-2021, which was confirmed by a PCR test (polymerase chain reaction). All these patients were observed in the NRCRM cardiology department before infection with the coronavirus. The comparison group consisted of 32 EW who did not suffer from COVID-19 and their age and examination dates corresponded to EWC. General clinical, laboratory, statistical methods and Doppler echocardiography were used for patients examination. In the post-covid period, EW-C observed a worsening of CHD clinical course, which consisted in an increase in the number of patients with severe functional class angina pectoris, with ventricular and supraventricular extrasystoles, as well as with more severe heart failure (HF). Since similar changes in the state of the cardiovascular system were found among EW who did not suffer from COVID-19, they can be attributed to the natural progression of CHD. In the EW-C group, there was an increase in the number of patients with atrial fibrillation (AF) by 4 times (up 37.5 %), while in the comparison group EW only by 1.1 times (up 3.1 %). The progression of CHD and HF in the examined patients was accompanied by an increase in the end-diastolic and end-systolic volumes of the left ventricle and the mass of the myocardium, the severity of which was not significantly different in patients with and without COVID-19. The number of post-covid patients with reduced ejection fraction (EF) during examination after COVID-19 increased by 31.3 %, and in the group of EW, which were examined at the same time, by 6.32 %. A significant increase in the number of patients with AF and a reduced EF in the EW-C compared with the EW can be attributed to the results of the SARS-CoV-2 virus influence on cardiovascular system.