Pathogenesis Of Coronary Heart Disease Research Articles

The effect of antiphospholipid antibodies on the frequency of extrasystoles in men with coronary heart disease and and myocardial infarction

Abstract Background Coronary heart disease (CHD) is one of the most socially significant diseases of the cardiovascular system. Acute myocardial infarction (MI) develops 10 years earlier in men than in women. Manifestation of MI in young men quite often happen without clinically significant stenosis of coronary vessels. And fatal arrhythmias are one of the main causes of death in patient with cardiovascular diseases. Purpose To evaluate the clinical and pathogenetic significance of antiphospholipid antibodies (aPL) in patients with MI and disorders of rythm. Methods 107 patients men (average age 51.2 ± 6.15 years) with CHD and MI were examined. The content of aPL IgG - antibodies to cardiolipin, phosphatidylserine, phosphatidylinositol, phosphatidylacetate in the blood serum were determined by enzyme-linked immunosorbent assay and electrocardiography Holter monitor 24 hours tests were done. Results aPL IgG were detected in 56 patients (52,3% of the total number of patients with MI), it concentration threshold 10 GPL U/ml in blood serum. The median age of first acute MI in men 56 years, according to the literary data. In our investigation average age of aPL positive patients is 44.8 ± 5.47 years. They had first MI on average 12 years earlier than general population. The level of aPL IgG in blood serum was higher in 1,7 times (19,3 ± 7,32 GPL U/ml and 11,4 ± 5,41 GPL U/ml (p <0.05) in patients with recurrent MI compared to one MI. Also the results of the study showed that the highest prevalence of polytopic extrasystoles is observed among aPL positive CHD patients with recurrent MI (68,3%) compared to one MI in anamnesis (26,3%). Moreover, 23.2% of people who had recurrent MI had ventricular extrasystole of high gradations. It is important to note, that іn patients with first Q-MI levels of aFL IgG were in 1.27 times higher (p<0.05) than in patients with first non-Q-MI. And the frequency of the polytopic extrasystoles was on 38% higher (p<0.01) іn patients with first Q-MI compared to patients with first non-Q-MI. Conclusion The results obtained by us indicate the possible involvement of the autoimmune factor, in particular aPL IgG, in the pathogenesis of CHD. Positive correlation of aPL IgG with the frequency of rhythm disorders indicates the severity of condition in men with CHD and MI in anamnesis and need for further research.

Circulating metabolites and coronary heart disease: a bidirectional Mendelian randomization

BackgroundNumerous studies have established a link between coronary heart disease and metabolic disorders. Yet, causal evidence connecting metabolites and Coronary Heart Disease (CHD) remains scarce. To address this, we performed a bidirectional Mendelian Randomization (MR) analysis investigating the causal relationship between blood metabolites and CHD.MethodsData were extracted from published genome-wide association studies (GWASs) on metabolite levels, focusing on 1,400 metabolite summary data as exposure measures. Primary analyses utilized the GWAS catalog database GCST90199698 (60,801 cases and 123,504 controls) and the FinnGen cohort (43,518 cases and 333,759 controls). The primary method used for causality analysis was random inverse variance weighting (IVW). Supplementary analyses included MR-Egger, weighted mode, and weighted median methods. Sensitivity analyses were conducted to evaluate heterogeneity and pleiotropy. Reverse MR analysis was employed to evaluate the direct impact of metabolites on coronary heart disease. Additionally, replication and meta-analysis were performed. We further conducted the Steiger test and colocalization analysis to reflect the causality deeply.ResultsThis study identified eight metabolites associated with lipids, amino acids and metabolite ratios that may influence CHD risk. Findings include: 1-oleoyl-2-arachidonoyl-GPE (18:1/20:4) levels: OR = 1.08; 95% CI 1.04–1.12; P = 8.21E-06; 1-palmitoyl-2-arachidonoyl-GPE (16:0/20:4) levels: OR = 1.07; 95% CI 1.04–1.11; P = 9.01E-05; Linoleoyl-arachidonoyl-glycerol (18:2/20:4): OR = 1.08; 95% CI 1.04–1.22; P = 0.0001; Glycocholenate sulfate: OR = 0.93; 95% CI 0.90–0.97; P = 0.0002; 1-stearoyl-2-arachidonoyl-GPE (OR = 1.07; 95% CI 1.03–1.11; P = 0.0002); N-acetylasparagine (OR = 1.04; 95% CI 1.02–1.07; P = 0.0030); Octadecenedioate (C18:1-DC) (OR = 0.93; 95% CI 0.90–0.97; P = 0.0004); Phosphate to linoleoyl-arachidonoyl-glycerol (18:2–20:4) (1) ratio (OR = 0.92; 95% CI 0.88–0.97; P = 0.0005).ConclusionThe integration of genomics and metabolomics offers novel insights into the pathogenesis of CHD and holds significant importance for the screening and prevention of CHD.

Role of inflammatory signaling pathways involving the CD40-CD40L-TRAF cascade in diabetes and hypertension-insights from animal and human studies.

CD40L-CD40-TRAF signaling plays a role in atherosclerosis progression and affects the pathogenesis of coronary heart disease (CHD). We tested the hypothesis that CD40L-CD40-TRAF signaling is a potential therapeutic target in hyperlipidemia, diabetes, and hypertension. In mouse models of hyperlipidemia plus diabetes (db/db mice) or hypertension (1mg/kg/d angiotensin-II for 7days), TRAF6 inhibitor treatment (2.5mg/kg/d for 7 or 14days) normalized markers of oxidative stress and inflammation. As diabetes and hypertension are important comorbidities aggravating CHD, we explored whether the CD40L-CD40-TRAF signaling cascade and their associated inflammatory pathways are expressed in CHD patients suffering from comorbidities. Therefore, we analyzed vascular bypass material (aorta or internal mammary artery) and plasma from patients with CHD with diabetes and/or hypertension. Our Olink targeted plasma proteomic analysis using the IMMUNO-ONCOLOGY panel revealed a pattern of step-wise increase for 13/92 markers of low-grade inflammation with significant changes. CD40L or CD40 significantly correlated with 38 or 56 other inflammatory targets. In addition, specific gene clusters that correlate with the comorbidities were identified in isolated aortic mRNA of CHD patients through RNA-sequencing. These signaling clusters comprised CD40L-CD40-TRAF, immune system, hemostasis, muscle contraction, metabolism of lipids, developmental biology, and apoptosis. Finally, immunological analysis revealed key markers correlated with comorbidities in CHD patients, such as CD40L, NOX2, CD68, and 3-nitrotyrosine. These data indicate that comorbidities increase inflammatory pathways in CHD, and targeting these pathways will be beneficial in reducing cardiovascular events in CHD patients with comorbidities.

Identification of Plasma Exosomes hsa_circ_0001360 and hsa_circ_0000038 as Key Biomarkers of Coronary Heart Disease.

Coronary heart disease (CHD) is the leading cause of death and disability worldwide. Accumulating evidence reveals that atherosclerosis (AS), characterized by systemic, chronic, and multifocal disease, and is the primary pathological basis of cardiovascular diseases, including CHD. However, the molecular underpinnings of CHD are still far from well understood. Our study attempted to identify aberrant plasma exosome-derived circRNAs and key exosomal circRNA biomarkers for CHD. The expression profiles of mRNAs, circRNAs, and lncRNAs in the blood exosomes of CHD patients and healthy controls were obtained from the exoRBase database. The corresponding miRNAs of the differentially expressed mRNAs, circRNAs, and lncRNAs were predicted via ENCORI and the miRcode database. LncRNAs/circRNAs and mRNAs with the cotargeted miRNAs were selected to construct an interaction network. Multiple machine learning algorithms have been used to explore potential biomarkers, followed by verification in patients with CHD using real-time quantitative reverse transcription-polymerase chain reaction (RT-qPCR). Based on the cutoff criterion of P < 0.05, we identified 85 differentially expressed circRNAs (4 upregulated and 81 downregulated), 43 differentially expressed lncRNAs (24 upregulated and 19 downregulated), and 312 differentially expressed mRNAs (55 upregulated and 257 downregulated). Functional enrichment analysis revealed that the differentially expressed mRNAs were involved mainly in neutrophil extracellular trap (NET) formation and the nucleotide-binding oligomerization domain- (NOD-) like receptor signaling pathway. Further analysis revealed that the DEGs in the circRNA/lncRNA-miRNA-mRNA interaction network were closely related to lipid and atherosclerotic signaling pathways. Hsa_circ_0001360 and hsa_circ_0000038 were identified as potential biomarkers for CHD based on three machine learning algorithms. The relative expression levels of hsa_circ_0001360 and hsa_circ_0000038 were significantly altered in plasma exosomes from patients with CHD. ROC curve analysis revealed that the areas under the curve (AUCs) were 0.860, 0.870, and 0.940 for hsa_circ_0001360, hsa_circ_0000038, and the two-gene combination, respectively. The circRNA/lncRNA-miRNA-mRNA interaction network might help to elucidate the pathogenesis of CHD. Hsa_circ_0001360 combined with hsa_circ_0000038 might be an important diagnostic biomarker.

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.

Role of low-density lipoprotein in mediating the effect of air pollution on coronary heart disease: a two-step multivariate Mendelian randomization study.

Air pollution is affecting the health of millions of people all over the world. The causal correlations of PM2.5, PM10, and nitrogen dioxide (NOx), as the main fine particulate matter, and coronary heart disease (CHD) are yet to be explored. Low-density lipoprotein (LDL) has been a principal factor in the pathogenesis of CHD. It is an interesting issue to consider whether LDL mediates the effect of air pollutants in CHD pathogenesis. A genome-wide association study (GWAS) on the European population, followed up from 2010 to 2018, involving over 400,000 participants, was based on a land-use regression model. The annual mean concentrations of major air pollutant particles, PM2.5 (n=423,796), PM10 (n=423,796), and NOx (n=456,380), were recorded. The large GWAS database of CHD covered over ten million SNPs with independent single nucleotide polymorphisms (SNPs). LDL database collected major biochemical blood parameters from over 400,000 patients (n=440,546). Taken together, we conducted independent two-sample Mendelian randomization (MR) analyses for the causality between air pollutants (PM2.5, PM10, and NOx) and CHD. Multivariate MR analysis was conducted using causal relationships to determine the direct effects of exposure on outcome. The fixed-effect inverse variance weighted (IVW2) method was mainly employed to assess this relationship, with a confidence interval of 95% for the odds ratio (OR). Also, MR-Egger, weighted median, maximum likelihood ratio method, and random-effects inverse variance-weighted (IVW1) method were adopted as supplementary methods. Two-sample MR results based on the IVW2 method suggested positive correlations between PM2.5 and CHD [OR 1.875 (1.279-2.748), p=0.001], PM10 and CHD [OR 2.586 (1.479-4.523), p=0.001], and NOx and CHD [OR 2.991 (2.021-4.427), p=4.37E-08]. The direct effect and mediating proportion were calculated using multivariable Mendelian randomization (MVMR). Lastly, the mediating proportions of LDL in the regulatory roles of PM2.5, PM10, and NOx in CHD were 2.82%, 4.73%, and 9.54%, respectively. PM2.5, PM10, and NOx share direct causal associations with CHD, and LDL performs a mediating role in this pathogenic process. Early prevention against air pollution (such as increasing green areas and reducing large-scale industrial dust emissions) and early lipid-lowering treatment can effectively prevent the occurrence of CHD.

PATHOGENESIS OF IMMUNE DYSFUNCTION IN THE SETTING OF METABOLIK SYNDROME IN CORONARY HEAT DISEASE. QUALIFYING SCENTIFYING WORK ON THE RIGHTS OF THE MANUSCRIPT

PATHOGENESIS OF IMMUNE DYSFUNCTION IN THE SETTING OF METABOLIK SYNDROME IN CORONARY HEAT DISEASE. QUALIFYING SCENTIFYING WORK ON THE RIGHTS OF THE MANUSCRIPT

MODERN VIEWS ON THE PATHOGENESIS OF IMMUNE DYSFUNCTION AGAINST THE BACKGROUND OF THE METABOLIC SYNDROME IN ISCHEMIC HEART DISEASE

Introduction. Today, the pathology of the cardiovascular system is one of the most common and fatal diseases. Cardiovascular diseases are the cause of disability among the younger and younger population. Taking into account the frequency of cardiovascular diseases, the severity of the course and their lethality, the study of this topic remains one of the most urgent problems of medicine, in particular cardiology.&#x0D; The aim of the study. Consider modern views on the pathogenesis of coronary heart disease against the background of metabolic syndrome and the role of the immune system.&#x0D; Conclusions. Ischemic heart disease is the leading cause of mortality in Ukraine and the world. In recent years, there has been convincing evidence of a significant prevalence of cardiovascular disease in patients with metabolic syndrome. The presence of concomitant metabolic syndrome in patients with coronary heart disease worsens the course of the underlying disease and has an unfavorable prognosis, and even fatal cases.&#x0D; Therefore, the detection of an increase in the level of body mass index, dyslipidemia, hyperglycemia, arterial hypertension in a patient strengthens the effects of each other, that is, they have a synergistic effect, and in general, the risk of developing CHD becomes quite high.&#x0D; IL-6 is one of the cytokines released by both macrophages and adipocytes and its levels have been shown to be increased in insulin resistance and obesity. In fact, IL-6 is known to regulate fat and glucose metabolism, mediating insulin resistance through various complex mechanisms. This cytokine acts on various tissues, leading to the metabolic effects of obesity. In the liver, IL-6 increases the production of acute phase reactants, including CRP. Several studies have demonstrated that high CRP levels have the strongest correlation with cardiac events, T2DM, and MS. IL-6 also contributes to a prothrombotic state by increasing the level of fibrinogen, another acute phase reactant. In addition, IL-6 targets other tissues, such as endothelial cells, to promote the expression of vascular cell adhesion molecules, leading to vascular wall atherosclerosis, inflammation, and dysfunction.&#x0D; These data support the role of IL-6 in the development of insulin resistance, but do not support the hypothesis that IL-6 is involved in β-cell failure.&#x0D; IL-18 is a pro-inflammatory cytokine associated with insulin resistance and T2DM risk. IL-18 stimulates the production of gamma interferon (IFN-γ), which, in turn, is probably involved in the pathogenesis of atherosclerosis. IL-18 is a cytokine that is a predictor of metabolic syndrome.&#x0D; TNFα is another cytokine produced in adipose tissue, mainly from local macrophages, and its production also varies with adipose tissue mass and correlates with insulin resistance, both hallmarks of MS. TNFα exerts its pathogenic effects by disrupting insulin signaling in adipocytes and hepatocytes through serine phosphorylation and inactivation of insulin receptors and downstream signaling molecules, leading to decreased metabolic effects of insulin. TNFα also contributes to insulin resistance by inducing hepatic lipolysis.

The mediation effect of HDL-C: Non-HDL-C on the association between inflammatory score and recurrent coronary events

BackgroundInflammation and lipids are both involved in the pathogenesis of coronary heart disease (CHD). However, the mediation effect of lipoproteins on the association between inflammation and recurrent coronary events in CHD patients remains unclear. MethodsThis was a retrospective study including CHD patients hospitalized in the Department of Cardiovascular Medicine in Sun Yat-sen Memorial Hospital between January 2011 and December 2012 with the endpoint of recurrent coronary events. The study calculated inflammatory score based on six serum inflammatory markers, including complement C3, complement C4, hyper-sensitive CRP, fibrinogen, D-dimer, and white blood cell count. Logistic regression analysis, subgroup analysis and mediation analysis were performed to assess the associations between inflammatory score and recurrent coronary events in different subpopulations and the identification of mediators. Inflammatory cytokine expression, cholesterol efflux capacity, and hepatic cholesterol influx were performed in additional CHD patients and healthy controls. ResultsThere were 191 CHD patients included in the analysis with a median inflammatory score of −0.78 (−2.17, 1.35) and 63 cases of recurrent coronary events. Subgroup logistic regression analysis demonstrated that inflammatory score was positively associated with recurrent coronary events only in the diabetic subgroup [OR: 1.241 (1.004, 1.534), P < 0.046]. HDL-cholesterol (HDL-C): non-HDL-C performed 46.74 % of negative mediation effect on this association. CHD patients had lower cholesterol efflux capacity than healthy controls, which was mediated by HDL: non-HDL ratio of 0.4. No difference was found in hepatic cholesterol influx between the two groups. ConclusionInflammatory score was associated with recurrent coronary events mediated by HDL-C: non-HDL-C ratio in diabetic CHD patients, indicating that lipoproteins might aggravate the inflammatory effect on atherosclerosis under hyperglycemia. Our findings suggested that anti-inflammatory and lipid-lowering therapies might be beneficial for this population.

CYP4V2 rs56413992 C > T was associated with the risk of coronary heart disease in the Chinese Han population: a case–control study

PurposeThe research aimed to detect the association between single nucleotide polymorphisms (SNPs) in CYP4V2 gene and coronary heart disease (CHD) risk.MethodsThis case–control study included 487 CHD subjects and 487 healthy individuals. Logistic regression was performed to analyze the connection between five SNPs in CYP4V2 (rs1398007, rs13146272, rs3736455, rs1053094, and rs56413992) and CHD risk, and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to evaluate the connection.ResultsAs a result, we found that rs56413992 T allele (OR = 1.36, 95% CI = 1.09–1.70, p = 0.007) and CT genotype (OR = 1.40, 95% CI = 1.06–1.83, p = 0.017) were significantly associated with an increased risk of CHD in the overall analysis. Precisely, rs56413992 was linked to an elevated risk of CHD in people aged > 60, males, smokers and drinkers. The study also indicated that rs1398007 was linked to an increased CHD risk in drinkers. In addition, rs1053094 was correlated with a decreased risk of CHD complicated with diabetes mellitus (DM), and rs1398007 was correlated with a decreased risk of CHD complicated with hypertension (HTN).ConclusionThis study was the first to experimentally demonstrate that CYP4V2 rs56413992 was associated with the risk of CHD, which will provide a certain reference for revealing the pathogenesis of CHD.

Characterization of lncRNA-associated ceRNA network to uncover novel potential biomarkers in coronary artery disease.

The purpose of this study was to construct a competitive endogenous RNA (ceRNA) network related to long non-coding RNA (lncRNAs) via the bioinformatics analysis, reveal the pathogenesis of coronary heart disease (CAD) and develop new biomarkers for CAD. The gene expression datasets of peripheral blood of CAD were downloaded from the Gene Expression Omnibus (GEO) database. The differentially expressed mRNAs, miRNAs and lncRNAs (DEmRNAs, DEmiRNAs and DElncRNAs) were identified. Subsequently, a ceRNA network involving lncRNAs, miRNAs, and mRNAs was built. Moreover, DElncRNAs in the cytoplasm were screened and a DElncRNA-associated ceRNA network was established. In total, 1860 DEmRNAs, 393 DElncRNAs and 20 DEmiRNAs were filtrated in patients with CAD compared with normal controls. Functional analysis suggested that DEmRNAs significantly enriched in CAD-related pathways, such as PI3K-Akt signaling pathways and MAPK signaling pathway. The ceRNA network contained 12 DEmiRNAs, 30 DElncRNAs and 537 DEmRNAs. Afterwards, the cytoplasm ceRNA network was consisted of 537 DEmRNAs, 12 DEmiRNAs and 12 DElncRNAs. Such as, up-regulated LncRNA-HOX transcript antisense RNA (HOTAIR) was interacted with down-regulated has-miR-326 and has-miR-1. The successful construction of lncRNA-associated ceRNA network is helpful to better clarify the pathogenesis of CAD and provide potential peripheral blood biomarkers for CAD.

In-hospital and 1-year outcomes of patients without modifiable risk factors presenting with acute coronary syndrome undergoing PCI: a sex-stratified analysis

Abstract Background The standard modifiable cardiovascular risk factors (SMuRFs: hypertension, diabetes mellitus, dyslipidemia, and cigarette smoking) are known to play a major role in the pathogenesis of coronary heart disease (CHD). Despite endeavors aiming at primary and secondary prevention of these risk factors, CHD has remained a leading cause of mortality and morbidity worldwide. A considerable proportion of patients admitted with acute coronary syndrome (ACS) have no SMuRFs, the outcomes of whom following percutaneous coronary intervention (PCI) are debated. Further, sex differences within this population have yet to be established. Purpose The present study aimed to evaluate the association between SMuRF-less status and post-PCI outcomes among patients with ACS. Further, we sought to determine possible sex differences in the post-PCI outcomes related to the SMuRF-less status. Methods This retrospective cohort study included 7847 patients with ACS who underwent PCI. The study outcomes were all-cause mortality and major adverse cardio-cerebrovascular events (MACCE). The association between the absence of SMuRFs (SMuRF-less status) and outcomes among all the patients and each sex was assessed using logistic and Cox proportional hazard regressions. A separate landmark analysis with the landmark (cutoff) set at 30 days after the index procedure was performed as well. Models were adjusted for age, sex, body mass index, chronic obstructive pulmonary disease, cerebrovascular accident, previous myocardial infarction, estimated glomerular filtration rate, ejection fraction, and left main disease. Results Approximately 11% of the study population had none of the SMuRFs. The SMuRF-less and SMuRF+ groups aged 63.10 ±8.91 (85.1% males) and 62.53 ± 10.91 years (74.9% males), respectively. During 12.13 [11.99-12.36] months of follow-up, the followings were respective event numbers in the SMuRF-less and SMuRF+ groups: all-cause mortality: 35 (4.1%) and 273 (3.9%); MACCE: 99 (11.6%) and 898 (12.8%). All-cause mortality (adjusted-hazard ratio (HR): 1.01, 95%CI: 0.88-1.46, P: 0.731), and MACCE (adjusted-HR: 0.93, 95%CI:0.81-1.12, P: 0.412) did not differ between patients with and without SMuRFs (Figure 1). Sex-stratified analyses recapitulated similar outcomes between SMuRF+ and SMuRF-less men. In contrast, SMuRF-less women had significantly higher all-cause mortality (adjusted-HR:1.41, 95%CI: 1.02-3.21, P: 0.008) than SMuRF+ women (Figure 1). Notably, following landmark analyses, this significant association among women disappeared (adjusted-HR: 0.99, 95%CI: 0.41-2.59, P:0.991), implying that its significance stemmed, to some extent, from higher 30-day mortality (Figure 1,2). Conclusions Almost one in 10 patients with ACS who underwent PCI had no SMuRFs. The absence of SMuRFs did not confer any benefit in terms of in-hospital mortality, one-year mortality, and MACCE. Even worse, SMuRF-less women paradoxically had an excessive risk of one-year mortality.

Analysis of Correlation Between Coronary Heart Disease and Genetic Polymorphism Detected by Gold Magnetic Nanoparticles Chromatography.

It aimed to explore the correlation of Glu504Lys locus mutation of aldehyde dehydrogenase-2 (ALDH2) with coronary heart disease (CHD) based on gold magnetic nanoparticles (GMNPs) chromatography and amplification refractory mutation system-PCR (ARMS-PCR). 120 CHD patients admitted to the cardiovascular Department of Wenling First People's Hospital affiliated to Wenzhou Medical University from December 2020 to December 2021 were selected as Case group and 80 non-CHD patients admitted during the same period were selected as Ctrl group. The venous blood and indexes of Total Cholesterol (TC), Triglyceride (TG), Low Density Lipoprotein Cholesterol (LDL-C), High Density Lipoprotein Cholesterol (HDL-C), and Fasting Blood Glucose (FBS) were collected. The ARMS-PCR GMNPs chromatography based on ARMS-PCR and immunochromatography assay was adopted to detect gene polymorphism of ALDH2. Correlation between ALDH2 gene polymorphism and risk factors of CHD was analyzed via logistic regression. In contrast to Ctrl group, the genotypes of GG, GA, and AA in Case group were evidently different (P < 0.05), and the frequency of A allelic gene was obviously increased (P < 0.05). Under the dominant model, frequency of GA + AA genotype in Case group was remarkably higher in contrast to Ctrl group (P < 0.05). Under the recessive model, there was no obvious difference in genotype frequency between two groups. In contrast to Ctrl group, TC, LDL-C, and FBS in Case group were notably increased (P < 0.05), while HDL-C was notably decreased (P < 0.05). The distribution frequency of abnormal LDL-C, HDL-C, and FBS in Case group was notably higher in contrast to Ctrl group (P < 0.05). LDL-C and FBS had no obvious effect on the genotypes and frequency distribution of alleles in CHD patients. However, the frequency distribution of genotypes of GA and AA and A allelic gene in patients with abnormal HDL-C was notably lower in contrast to those with normal HDL-C (P < 0.05). Logistic regression analysis showed that abnormal HDC-C with A allelic gene were independent risk factors for CHD (P = 0.001, OR = 1.934). The gene polymorphism of Glu504Lys locus of ALDH2 was closely related to the pathogenesis of CHD, A allelic gene may be a susceptibility gene for CHD, and patients with abnormal HDC-C and carried A allelic gene had relatively higher incidence of CHD.

High dietary inflammatory index is associated with decreased plaque stability in patients with coronary heart disease

Coronary plaque stability is a key pathological mechanism of coronary heart disease (CHD). Inflammation is recognized as a key factor of coronary plaque stability. The dietary inflammatory index (DII) is calculated from 21 dietary nutrients to predict the inflammation potential of an individual's diet. We hypothesized that high DII may be associated with decreased coronary plaque stability in CHD patients; therefore, this study aimed to evaluate the association between DII and plaque stability in patients with CHD. This cross-sectional study included 314 patients with CHD. DII was calculated based on food frequency questionnaires. Plaque stability was measured with optical coherence tomography. The DII ranged from –1.41 to 3.04. After adjusting for confounding factors, higher DII scores were associated with unstable plaque characteristics including thin-capped fibroatheroma (odds ratio [OR], 3.60; 95% confidence interval [CI], 1.78–7.29), macrophage infiltration (OR, 2.16; 95% CI, 1.01–4.61), and plaque rupture (OR, 3.55; 95% CI, 1.73–7.29). Mediation analyses revealed that DII was important mediator of the relationship between plaque stability and food intake including soybeans and nuts, fish and shrimp, eggs (P < .05). The present study confirmed that higher DII is significantly associated with decreased plaque stability in CHD patients, suggesting an important protective role of anti-inflammatory diets in the pathogenesis of CHD.

Association of Circulating Matrix Metalloproteinase-9 and the Risk of Coronary Heart Disease in Young Smokers

Introduction: Smoking causes cardiovascular risk which may alter the stability between the production and degradation of the extracellular matrix. Matrix metalloproteinase-9 (MMP-9) is a zinc-containing endopeptidase that degrades the extracellular matrix and plays a vital role in tissue remodeling. As a result, elevated serum MMP-9 levels produced by smoking, particularly at young age, raise the risk of future CHD. So this study aims to find out the possible relationship between circulating MMP-9 and the risk of cardiovascular disease in young smokers. Methods: The study was conducted on smokers with CHD subjects attending cardiology and medicine OP of the SRM Medical College Hospital and research center Tamil Nadu, India. The study group was divided into three groups. Group 1 includes 120 healthy controls as nonsmokers, Group 2 includes 120 smokers with Coronary heart disease (CHD), and Group 3 includes 120 smokers with diabetes and CHD subjects in the age group of 20-55 years. Serum MMP-9, hs-CRP, and APO-E levels were measured using the ELISA method and the lipid level was measured enzymatically using AU480 automatic analyzer (back man coulter). Results: The mean serum MMP-9, hs-CRP, and APO-E levels were significantly higher in both groups (p&lt;0.05) when compared to controls. The study also shows a significant positive association between MMP-9 with hs-CRP, APO-E, smoking burden, and smoking intensity. Conclusion: The study concludes a significant association exists between cigarette smoking with MMP-9 and also relative exposure to circulating inflammation markers plays a potential role in the pathogenesis of CHD.

Correlation of mitochondrial tRNA variants with coronary heart disease in a Chinese pedigree

To explore the correlation of mitochondrial DNA (mtDNA) variants and coronary heart disease (CHD) in a Chinese pedigree and the possible molecular mechanisms. A Chinese pedigree featuring matrilineal inheritance of CHD who visited Hangzhou First People's Hospital in May 2022 was selected as the study subject. Clinical data of the proband and her affected relatives was collected. By sequencing the mtDNA of the proband and her pedigree members, candidate variants were identified through comparison with wild type mitochondrial genes. Conservative analysis among various species was conducted, and bioinformatics software was used to predict the impact of variants on the secondary structure of tRNA. Real-time PCR was carried out to determine the copy number of mtDNA, and a transmitochondrial cell line was established for analyzing the mitochondrial functions, including membrane potential and ATP level. This pedigree had contained thirty-two members from four generations. Among ten maternal members, four had CHD, which yielded a penetrance rate of 40%. Sequence analysis of proband and her matrilineal relatives revealed the presence of a novel m.4420A>T variant and a m.10463T>C variant, both of which were highly conserved among various species. Structurally, the m.4420A>T variant had occurred at position 22 in the D-arm of tRNAMet, which disrupted the 13T-22A base-pairing, while the m.10463T>C variant was located at position 67 in the acceptor arm of tRNAArg, a position critical for steady-state level of the tRNA. Functional analysis revealed that patients with the m.4420A>T and m.10463T>C variants exhibited much fewer copy number of mtDNA and lower mitochondrial membrane potential (MMP) and ATP contents (P < 0.05), which were decreased by approximately 50.47%, 39.6% and 47.4%, respectively. Mitochondrial tRNAMet 4420A>T and tRNAArg 10463T>C variants may underlay the maternally transmitted CHD in this pedigree, which had shown variation in mtDNA homogeneity, age of onset, clinical phenotype and other differences, suggesting that nuclear genes, environmental factors and mitochondrial genetic background have certain influence on the pathogenesis of CHD.

Sex-specific association between microvascular health and coagulation parameters: the Netherlands Epidemiology of Obesity study

BackgroundMicrovascular dysfunction is a growing determinant of sex differences in coronary heart disease (CHD). Dysregulation of the coagulation system is involved in CHD pathogenesis and can be induced by endothelial glycocalyx (EG) perturbation. However, little is known about the link between EG function and coagulation parameters in population-based studies on sex specificity. ObjectivesWe sought to examine the sex differences in the relationship between EG function and coagulation parameters in a middle-aged Dutch population. MethodsUsing baseline measurements of 771 participants from the Netherlands Epidemiology of Obesity study (age, 56 years [IQR, 51-61 years]; 53% women; body mass index, 27.9 kg/m2 [IQR, 25.1-30.9 kg/m2]), associations between glycocalyx-related perfused boundary region (PBR) derived using sidestream dark-field imaging and coagulation parameters (factor [F]VIII/IX/XI; thrombin generation parameters; and fibrinogen) were investigated using linear regression analyses, adjusting for possible confounders (including C-reactive protein, leptin, and glycoprotein acetyls), followed by sex-stratified analyses. ResultsThere was a sex difference in the associations between PBR and coagulation parameters. Particularly in women, 1-SD PBR (both total and feed vessel, indicating poorer glycocalyx status) was associated with higher FIX activity ([1.8%; 95% CI, 0.3%-3.3%] and [2.0%; 95% CI, 0.5%-3.4%], respectively) and plasma fibrinogen levels ([5.1 mg/dL; 95% CI, 0.4-9.9 mg/dL] and [5.8 mg/dL; 95% CI, 1.1-10.6 mg/dL], respectively). Furthermore, 1-SD PBRcapillary was associated with higher FVIII activity (3.5%; 95% CI, 0.4%-6.5%) and plasma fibrinogen levels (5.3 mg/dL; 95% CI, 0.6-10.0 mg/dL). ConclusionWe revealed a sex-specific association between microcirculatory health and procoagulant status, which suggests that microvascular health be considered during early development of CHD in women.

The Reversion of the Epigenetic Signature of Coronary Heart Disease in Response to Smoking Cessation.

Coronary heart disease (CHD) is the leading cause of death worldwide. However, current diagnostic tools for CHD, such as coronary computed tomography angiography (CCTA), are poorly suited for monitoring treatment response. Recently, we have introduced an artificial-intelligence-guided integrated genetic-epigenetic test for CHD whose core consists of six assays that determine methylation in pathways known to moderate the pathogenesis of CHD. However, whether methylation at these six loci is sufficiently dynamic to guide CHD treatment response is unknown. To test that hypothesis, we examined the relationship of changes in these six loci to changes in cg05575921, a generally accepted marker of smoking intensity, using DNA from a cohort of 39 subjects undergoing a 90-day smoking cessation intervention and methylation-sensitive digital PCR (MSdPCR). We found that changes in epigenetic smoking intensity were significantly associated with reversion of the CHD-associated methylation signature at five of the six MSdPCR predictor sites: cg03725309, cg12586707, cg04988978, cg17901584, and cg21161138. We conclude that methylation-based approaches could be a scalable method for assessing the clinical effectiveness of CHD interventions, and that further studies to understand the responsiveness of these epigenetic measures to other forms of CHD treatment are in order.

Case of acute recurrent myocardial infarction in a child

Information on the essential aspects of prevalence, etiology and pathogenesis of coronary heart disease, which is the leading cause of death in the world, is given in this article. It is emphasized that the incidence of ischemic coronary events is the result of a complex sequence of pathogenetic links, which involves the formation of atherosclerotic lesions and destabilization as the primary provoking factor. Purpose - the attraction of the medical community attention to the problem of ischemic heart disease in children. A clinical case of recurrent myocardial infarction in a child who was examined and treated at the MNPE «Ivano-Frankivsk Regional Children’s Clinical Hospital of the Ivano-Frankivsk Regional Council», is described here. The key points of the patient’s complaints, anamnesis of life and this disease are described, the data of the objective condition at the hospitalization and during dynamic observation of the child, which showed the signs of left ventricular overload, coronary blood flow disorder, dilatation of the left heart ventricles, decreased left ventricular contractility. The data of the main indices of laboratory and instrumental methods of research, including X-ray diagnostic methods, performed not only on the basis of the department, but also in the Scientific-Practical Medical Center of Pediatric Cardiology and Cardiac Surgery of the Ministry of Health of Ukraine (Kyiv). The treatment of this clinical case in the child is described in this article. The data of dynamic observation are given. The discussion and conclusions emphasize the problem of coronary insufficiency in pediatrics, which requires clinical understanding, the choice of the correct diagnostic algorithm and qualified medical care. The study was performed in accordance with the principles of the Declaration of Helsinki. Informed consent of the child’s parents was obtained for the research conduction. No conflict of interests was declared by the authors.

Exogenous exposures shape genetic predisposition to lipids, Alzheimer's, and coronary heart disease in the MLXIPL gene locus.

Associations of single nucleotide polymorphisms (SNPs) of the MLXIPL lipid gene with Alzheimer's (AD) and coronary heart disease (CHD) and potentially causal mediation effects of their risk factors, high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG), were examined in two samples of European ancestry from the US (22,712 individuals 587/2,608 AD/CHD cases) and the UK Biobank (UKB) (232,341 individuals; 809/15,269 AD/CHD cases). Our results suggest that these associations can be regulated by several biological mechanisms and shaped by exogenous exposures. Two patterns of associations (represented by rs17145750 and rs6967028) were identified. Minor alleles of rs17145750 and rs6967028 demonstrated primary (secondary) association with high TG (lower HDL-C) and high HDL-C (lower TG) levels, respectively. The primary association explained ~50% of the secondary one suggesting partly independent mechanisms of TG and HDL-C regulation. The magnitude of the association of rs17145750 with HDL-C was significantly higher in the US vs. UKB sample and likely related to differences in exogenous exposures in the two countries. rs17145750 demonstrated a significant detrimental indirect effect through TG on AD risk in the UKB only (βIE = 0.015, pIE = 1.9 × 10-3), which suggests protective effects of high TG levels against AD, likely shaped by exogenous exposures. Also, rs17145750 demonstrated significant protective indirect effects through TG and HDL-C in the associations with CHD in both samples. In contrast, rs6967028 demonstrated an adverse mediation effect through HDL-C on CHD risk in the US sample only (βIE = 0.019, pIE = 8.6 × 10-4). This trade-off suggests different roles of triglyceride mediated mechanisms in the pathogenesis of AD and CHD.