To investigate the association of ABCG1, GALNT2 and HMGCR genes promoter DNA methylation with coronary heart disease (CHD) and explore the interaction between their methylation status and the CHD patients' clinical characteristics in Han Chinese population. Methylation-specific polymerase chain reaction (MSP) technology was used to examine the role of the aberrant gene promoter methylation in CHD in Han Chinese population. A total of 85 CHD patients and 54 participants without CHD confirmed by angiography were recruited. 82.8% of the participants with ABCG1 gene promoter hypermethylation have CHD, while only 17.4% of the participants without hypermethylation have it. The average age of the participants with GALNT2 gene promoter hypermethylation is 62.10±8.21, while that of the participants without hypermethylation is 57.28±9.87; in the former group, 75.4% of the participants have CHD, compared to only 50% in the latter group. As for the HMGCR gene, the average age of the participants with promoter hypermethylation is 63.24±8.10 and that of the participants without hypermethylation is 57.79±9.55; its promoter hypermethylation is likely to be related to smoking. Our results indicated a significant statistical association of promoter methylation of the ABCG1 gene with increased risk of CHD (OR = 19.966; 95% CI, 7.319–54.468; P^*<0.001; P^*: adjusted for age, gender, smoking, lipid level, hypertension, and diabetes). Similar results were obtained for that of the GALNT2 gene (OR = 2.978; 95% CI, 1.335–6.646; P^* = 0.008), but not of HMGCR gene (OR = 1.388; 95% CI, 0.572–3.371; P^* = 0.469). The present work provides evidence to support the association of promoter DNA methylation status with the risk profile of CHD. Our data indicates that promoter DNA hypermethylation of the ABCG1 and GALNT2 genes, but not the HMGCR gene, is associated with an increased risk of CHD. CHD, smoking and aging are likely to be the important factors influencing DNA hypermethylation.

Coronary artery disease (CAD) is the leading cause of human morbidity and mortality worldwide. Innovative diagnostic biomarkers are a pressing need for this disease. miRNAs profiling is an innovative method of identifying biomarkers for many diseases and could be proven as a powerful tool in the diagnosis and treatment of CAD. We performed miRNA microarray analysis from the plasma of three CAD patients and three healthy controls. Subsequently, we performed quantitative real-time PCR (qRT-PCR) analysis of miRNA expression in plasma of another 67 CAD patients and 67 healthy controls. We identified two miRNAs (miR-206 and miR-574-5p) that were significantly up-regulated in CAD patients as compared with healthy controls (P<0.05). The receiver operating characteristic (ROC) curves indicated these two miRNAs had great potential to provide sensitive and specific diagnostic value for CAD.

Coronavirus disease-2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), poses an enormous challenge to the medical system, especially the lack of safe and effective COVID-19 treatment methods, forcing people to look for drugs that may have therapeutic effects as soon as possible. Some old drugs have shown clinical benefits after a few small clinical trials that attracted great attention. Clinically, however, many drugs, including those currently used in COVID-19, such as chloroquine, hydroxychloroquine, azithromycin, and lopinavir/ritonavir, may cause cardiotoxicity by acting on cardiac potassium channels, especially hERG channel through their off-target effects. The blocking of the hERG channel prolongs QT intervals on electrocardiograms; thus, it might induce severe ventricular arrhythmias and even sudden cardiac death. Therefore, while focusing on the efficacy of COVID-19 drugs, the fact that they block hERG channels to cause arrhythmias cannot be ignored. To develop safer and more effective drugs, it is necessary to understand the interactions between drugs and the hERG channel and the molecular mechanism behind this high affinity. In this review, we focus on the biochemical and molecular mechanistic aspects of drug-related blockade of the hERG channel to provide insights into QT prolongation caused by off-label use of related drugs in COVID-19, and hope to weigh the risks and benefits when using these drugs.

The endothelial-mesenchymal transition (EndMT) is involved in the development of atherosclerosis (AS) and is a key process in vascular endothelial injury. Oxidative stress, inflammation, and apoptosis are common causes of EndMT, and EndMT progression can further accelerate the development of AS. The metabolite trimethylamine N-oxide (TMAO) is produced by the gut microbiome and is implicated in the development of several diseases, including diabetes and chronic kidney disease. However, the impact of TMAO on transforming growth factor β1(TGF-β1)-induced EndMT remains unclear. We hypothesize that TMAO exacerbates plaque formation and cardiac function impairment by promoting EndMT. Herein, we showed that high serum TMAO levels caused plaque formation, cardiac function damage and haemodynamic changes in ApoE^-/- mice. In vitro, TMAO upregulated mesenchymal markers and downregulated endothelial markers in HAECs. Furthermore, TMAO increased the migratory capacity of EndMT cells. Mechanistically, we found that PERK downregulation could alleviate TMAO-induced oxidative stress, EndMT, plaque formation and cardiac function damage. Further study showed that activated transcription factor 3 (ATF3), the downstream molecule of protein kinase RNA-like endoplasmic reticulum kinase (PERK), could bind with TGF-β1/2 and affect EndMT. Overall, TMAO promotes EndMT, possibly through the PERK-eIF2α-ATF4-CHOP or the PERk-eIF2α-ATF3-TGF-β signalling pathways.

The goal of our study is to assess the contribution of KIF6 Trp719Arg to both the risk of CHD and the efficacy of statin therapy in CHD patients. Meta-analysis of 8 prospective studies among 77,400 Caucasians provides evidence that 719Arg increases the risk of CHD (P<0.001, HR = 1.27, 95% CI = 1.15–1.41). However, another meta-analysis of 7 case-control studies among 65,200 individuals fails to find a significant relationship between Trp719Arg and the risk of CHD (P = 0.642, OR = 1.02, 95% CI = 0.95–1.08). This suggests that the contribution of Trp719Arg to CHD varies in different ethnic groups. Additional meta-analysis also shows that statin therapy only benefit the vascular patients carry 719Arg allele (P<0.001, relative ratio (RR) = 0.60, 95% CI = 0.54–0.67). To examine the role of this genetic variant in CHD risk in Han Chinese, we have conducted a case-control study with 289 CHD cases, 193 non-CHD controls, and 329 unrelated healthy volunteers as healthy controls. On post hoc analysis, significant allele frequency difference of 719Arg is observed between female CHD cases and female total controls under the dominant model (P = 0.04, χ² = 4.228, df = 1, odd ratio (OR) = 1.979, 95% confidence interval (CI) = 1.023–3.828). Similar trends are observed for post hoc analysis between female CHD cases and female healthy controls (dominant model: P = 0.04, χ² = 4.231, df = 1, OR = 2.015, 95% CI = 1.024–3.964). Non-genetic CHD risk factors are not controlled in these analyses. Our meta-analysis demonstrates the role of Trp719Arg of KIF6 gene in the risk of CHD in Caucasians. The meta-analysis also suggests the role of this variant in statin therapeutic response in vascular diseases. Our case-control study suggests that Trp719Arg of KIF6 gene is associated with CHD in female Han Chinese through a post hoc analysis.