Abstract:In recent years, methylation of RNA has attracted much attention due to its important role in post-transcriptional regulation of genes. Among them, the m6A modification of RNA is the highest methylation modification except for the 5′cap structure in mRNA. m6A related enzymes are divided into three categories:RNA methyltransferases, RNA demethylases and m6A binding proteins, which play roles in catalytic methylation modification, removal of methylation modification and identification of the methylation site of N6-adenosine, respectively. Then they can help participate in the downstream gene translation, mRNA degradation, control the speed of the RNA nuclear export, and so on. Among these enzymes, methyltransferase-like 3 (METTL3), as the core component of RNA methylation transferases, plays a role in regulating the overall m6A modification of cellular RNA. Cardiovascular diseases are a kind of diseases greatly affected by environmental factors, whereas the latter could affect the occurrence and development through epigenetic related mechanism. Therefore, epigenetics has become a hot issue in the study of cardiovascular disease. The purpose of this review is to briefly summarize the research work related to METTL3 in cardiovascular diseases, which is expected to help the subsequent scientific research and clinical workers to understand the mechanism of m6A in cardiovascular disease development.

Abstract:Atherosclerosis (As) is one of the important factors leading to high mortality and disability rate of cardiovascular and cerebrovascular diseases. Since its pathogenesis and heterogeneity distribution are still not clear, the “early detection, diagnosis and treatment” of As in vivo remains a great challenge. Fluorescence imaging is widely used in basic and clinical medical fields such as disease pathogenesis research, drug efficacy evaluation, and surgical navigation, because of its unique advantages such as sensitivity, noninvasive, high spatial and temporal resolution and real-time in situ, especially near-infrared fluorescence imaging with lower background interference and deeper tissue penetration, and it provides a new opportunity for the detection and treatment of the development and progression of As. Fluorescence imaging has attracted more and more attention in the research of As. This paper reviews the new progress of fluorescence imaging technology in the study of As.

Abstract:Aim To explore whether mitogen-activated protein kinase-interacting kinase-2 (MNK2) facilitates cardiac repair by inhibiting cardiomyocyte apoptosis induced by hypoxia and reoxygenation in mice and its underlying molecular mechanisms. Methods The cardiomyocyte hypoxia/reoxygenation (H/R) model was induced in vitro. The experimental groups were H/R+virus vector group, H/R+MNK2 overexpression adenovirus group and H/R+siRNA-MNK2 knockdown adenovirus group. Adult mouse heart ischemia/reperfusion (I/R) injury model was induced in vivo. The experimental groups were I/R+virus vector group and I/R+MNK2 overexpression adenovirus group. Western blot was used to detect the expressions of MNK2, p-MNK2,Bü lymphoma 2 related protein (Bax) and B lymphoma 2 (Bcl-2); Terminal deoxynucleotidyl transferase mediated nick end labeling (TUNEL) was used to detect the level of cardiomyocyte apoptosis; Echocardiography was used to detect cardiac function. Subsequently, the primary cardiomyocytes of H/R+MNK2 overexpression adenovirus group and H/R+virus vector group were used to perform RNA sequencing (RNA-seq). Differential gene enrichment and Kyoto Encyclopedia of genes and genomes (KEGG) were used to analyze the mechanism of anti-apoptotic effect of MNK2. The related cAMP signal pathway was found. Finally, the regulatory relationship between MNK2 and cAMP/PKA-CREB signal pathway was explored through rescue experiments. Results The expression level of p-MNK2 was significantly increased in H/R model group and I/R model group than that in the control group. In vitro, overexpression of MNK2 significantly increased the levels of MNK2 and p-MNK2 expression in cardiomyocytes. At the same time, it was found that the expression of apoptosis index protein Bcl-2 increased, Bax decreased, and the number of apoptotic cardiomyocytes reduced by 69.16% (all P＜0.05); Transfection of siRNA-MNK2 decreased the expression of Bcl-2, increased the expression of Bax significantly; In vivo, compared with the I/R+virus vector group, the cardiac function of the I/R+MNK2 overexpression adenovirus group showed no significant difference at 1 hour after I/R, while recovered significantly at 3 days after operation, in which the ejection fraction increased by 36.24% and the short axis shortening rate increased by 46.19% (all P＜0.05); TUNEL staining showed that myocardial apoptosis in I/R+MNK2 overexpression group decreased significantly by 28.65% (P＜0.05). Subsequently, the involvement of cAMP signaling pathway was confirmed by RNA-seq, bioinformatics analysis and relevant experimental verification. Experiments showed that overexpression of MNK2 activated cAMP/PKA-CREB signal pathway and the inhibition of PKA would enhance cardiomyocyte apoptosis inhibited by the overexpression of MNK2. Conclusion Overexpression of MNK2 can significantly inhibit apoptosis of mouse cardiomyocytes after H/R and improve cardiac function by activating cAMP/PKA-CREB signaling pathway.

Abstract:Aim To establish a rapid and convenient cardiovascular biomarker protein one-step point-of-care testing (POCT) chip system. Methods A polyethylene glycol methyl ether methacrylate layer (PEGMEMA) with anti-nonspecific adsorption property was synthesized on the cyclic olefin copolymer(COC) sheet by photochemical reaction, and non-contact inkjet printing was performed on the modified surface to form antibody microarrays. The contact angles and grafting densities of the surface were explored with several monomer concentrations after irradiated under UV light for certain time periods. The modified surface structure was characterized by atomic force microscopy and infrared spectroscopy, and the protein adsorption on the surface before and after photochemical reaction was compared. The appropriate antibody inkjet printing concentration and adjuvant conditions were further explored. Finally immobilized antibodies and fluorescently labeled soluble antibodies of the growth-stimulated expression gene 2 protein (ST2), a biomarker of cardiovascular damage, were printed on the modified surface. Results When the PEGMEMA monomer concentration was 30% by mass and the illumination time was 4 min, the contact angle reached the minimum as 38.5°, and the grafting density was up to 68.47 μg/cm². Atomic force microscopy and infrared spectroscopy showed that carbonyl and ether groups were successfully introduced into the surface. The amount of non-specific protein adsorption was reduced after surface grafting of PEGMEMA. The highest immobilization efficiency was obtained when the immobilized antibody concentration was 80 mg/L.Compared with polyethylene glycol (PEG) with several molecular weights, the effective binding efficiency of soluble antibody onto immobilized antibody microarray was higher when trehalose was used as an excipient. When the ST2 concentration was 10 mg/L, the binding of the soluble antibody on the immobilized antibody microarray after dissolution could be observed. Conclusion The anti-nonspecific adsorption of PEGMEMA was modified on the surface of the COC plastic sheet by photochemical reaction, and physically immobilized antibodies and the fluorescently labeled soluble antibodies were printed on the modified sheet surface, fabricated a protein chip system which is convenient to rapidly detect cardiovascular biomarkers, to advance cardiovascular precision medicine.

Abstract:Aim To investigate the effect of lncRNA-BC200 on the inflammation and apoptosis of nerve cells induced by Aβ₂₅-35 and its possible mechanism. Methods The nerve cells PC12 were divided into NC group (conventional cell culture) and 0,0, 40 μmol/L Aβ₂₅-35 groups (cells were treated with 0,0, 40 μmol/L Aβ₂₅-35 for 24 h), and then cell apoptosis was detected by flow cytometry. qRT-PCR method was used to detect the expression of lncRNA-BC200 in cells. The PC12 cells were divided into NC group (cells were routinely cultured), Aβ₂₅-35 group (PC12 cells were intervened with 20 μmol/L Aβ₂₅-35 for 24 h), si-NC+Aβ₂₅-35 group (PC12 cells were transfected with si-NC and then intervened with 20 μmol/L Aβ₂₅-35 for 24 h), si-lncRNA-BC200+Aβ₂₅-35 group (PC12 cells were transfected with si-lncRNA-BC200 and then intervened with 20 μmol/L Aβ₂₅-35 for 24 h) and TNF-α+si-lncRNA-BC200+Aβ₂₅-35 group (PC12 cells were transfected with si-lncRNA-BC200 and then co-intervened with 20 μmol/L Aβ₂₅-35 and 20 μg/L tumor necrosis factor (TNF-α) for 24 h). Flow cytometry was used to detect cell proliferation activity and apoptosis, ELISA was used to detect the expression of TNF-α, interleukin-6 (IL-6) and interferon-γ (IFN-γ) in the cell culture supernatant, and Western blot was used to detect the protein expression of cleaved-Caspase-3, p-p65 and p-IκBα in the cells. Results The apoptosis rate of PC12 cells and the expression of lncRNA-BC200 were higher in 0,0, 40 μmol/L Aβ₂₅-35 groups than NC group. The protein expression of cleaved-Caspase-3, p-p65 and p-IκBα and the levels of TNF-α, IL-6 and IFN-γ in Aβ₂₅-35 group cells were all higher than NC group. The apoptotic rate of PC12 cells, the protein expression of cleaved-Caspase-3, p-p65 and p-IκBα, and the levels of TNF-α, IL-6 and IFN-γ were all lower in the si-lncRNA-BC200+Aβ₂₅-35 group than Aβ₂₅-35 group. The apoptotic rate of PC12 cells, the protein expression of cleaved-Caspase-3, p-p65 and p-IκBα, and the levels of TNF-α, IL-6 and IFN-γ in the TNF-α+si-lncRNA-BC200+Aβ₂₅-35 group were all higher than the si-lncRNA-BC200+Aβ₂₅-35 group. Conclusion Knockdown of lncRNA-BC200 may inhibit Aβ₂₅-35-induced neuronal cell PC12 secretion of inflammatory factors and apoptosis by inhibiting the activation of NF-κB signaling pathway.

Abstract:Aim To explore the relationship between serum Sclerostin, Endocan and type 2 diabetes mellitus (T2DM) subclinical atherosclerosis (SAS). Methods 117 cases of T2DM patients who were admitted to Chenzhou First People's Hospital from February 2019 to March 2021 were selected as the research objects, and the occurrence of SAS in T2DM patients was counted. The correlation between serum Sclerostin, Endocan and common carotid artery intima-media thickness (CIMT) were analyzed. The influencing factors of SAS in T2DM patients were analyzed. The value of serum Sclerostin and Endocan in predicting the occurrence of SAS in T2DM patients was analyzed. Results 68 cases (58.12%) developed SAS among the 117 cases of T2DM patients. The results of univariate analysis showed that the occurrence of SAS in T2DM patients was related to age, course of T2DM, complicated with hypertension, fasting plasma glucose(FPG), total cholesterol (TC), low density lipoprotein cholesterol (LDLC), fibrinogen, CIMT, Sclerostin and Endocan (P＜0.05). The results of multivariate Logistic regression analysis showed that age, LDLC, CIMT, FPG, Sclerostin and Endocan were all influencing factors for the occurrence of SAS in T2DM patients (P＜0.05). The results of Pearson correlation analysis showed that Sclerostin and Endocan were positively correlated with CIMT (P＜0.05). Receiver operating characteristic (ROC) curve analysis showed that the area under the curve (AUC) of serum Sclerostin, Endocan and their combination in predicting the occurrence of SAS in T2DM patients were 0.771 (95%CI: 0.616～0.926), 0.712 (95%CI: 0.493～0.929) and 0.827 (95%CI: 0.657～0.988), respectively. Conclusions T2DM patients have a higher risk of developing SAS. Serum Sclerostin and Endocan are related to the occurrence of SAS in T2DM patients. The combination of the two has a high efficiency in predicting the occurrence of SAS in T2DM patients.

Abstract:Aim To explore the effect of hyperuricemia on the severity of coronary artery disease and clinical prognosis after percutaneous coronary intervention(PCI)of patients with acute coronary syndrome(ACS)and hypertension.Methods 422 patients were included who were diagnosed with ACS and hypertension after PCI. According to the diagnostic criteria of hyperuricemia, these patients were divided into hyperuricemia group (208 patients) and normal-level serum uric acid (UA) group (214 patients), and the general clinical characteristics, coronary angiography results and major adverse cardiovascular events within 1 year were analyzed. Univariate and multivariate Logistic regression models were used to explore the related risk factors of multi-vessel coronary artery disease and total MACE within 1 year. Furthermore, the serum UA levels of all patients were grouped according to the interquartile range to explore the dose-effect relationship between serum UA levels and total MACE within 1 year, severity of coronary artery disease. Spearman correlation analysis was used to analyze the correlation between serum UA level and Gensini score. With all-cause death as the ending event, Kaplan-Meier survival curve was used to describe the cumulative survival of two groups within 1 year (Log-rank test).Results Compared with normal-level serum uric acid group, multi-vessel coronary artery disease and non-criminal vascular occlusion were more common, and the Gensini scores were also higher in the hyperuricemia group (P＜0.05). Among the MACE that occurred within one year, the incidence of all-cause death, PCI or coronary artery bypass grafting (CABG) for myocardial infarction or angina pectoris, conservative medication treatment for myocardial infarction or angina pectoris, and total MACE were higher (P＜0.05). Univariate and multivariate Logistic regression analysis models showed that hyperuricemia was still an independent risk factor for total MACE within 1 year and multi-vessel coronary artery disease before and after adjusting for confounding factors (P＜0.05). The severity of coronary artery disease and the incidence of total MACE increased significantly with the increase of serum uric acid levels (P＜0.05). And the one-year all-cause death cumulative survival rate of hyperuricemia group decreased significantly(Log-rank test, P＝0.043) compared with patients with normal-level serum uric acid group. Conclusion Hyperuricemia is an independent risk factor for multi-vessel coronary artery disease and total MACE in patients with ACS and hypertension after PCI, and patients with hyperuricemia had a lower survival rate compared with patients with normal-level serum uric acid.

Abstract:Aim To explore the ability of serum growth differentiation factor-15 (GDF-15) and the ABC (age, biomarkers, clinical history) bleeding risk score based on this in predicting hemorrhage events in elderly (age≥65 years) patients with non-valvular atrial fibrillation (NVAF) after oral administration of non-vitamin K antagonist oral anticoagulants (NOAC). Methods Elderly inpatients who were first diagnosed as NVAF and treated with NOAC were selected. The GDF-15 concentration in serum was analyzed and clinical data were collected in each enrolled patient. The ABC bleeding risk score was calculated, which is essential on biomarkers including GDF-15, and HAS-BLED bleeding risk score. The patients were divided into groups according to the occurrence of various bleeding events(major bleeding (MB), clinically relevant non-major gastrointestinal bleeding (CRNM-GIB),minor bleeding, and no bleeding events) during follow-up. The ABC bleeding risk score and HAS-BLED bleeding risk score were evaluated and compared for predicting various degrees of bleeding events groups. Results During the (19.92±6.83) months follow-up period, 49 cases (49/2,4.5%) had bleeding events, including 3 cases of cerebral hemorrhage, 19 cases of CRNM-GIB, and 27 cases of minor bleeding. Receiver operating characteristic (ROC)curve showed that serum GDF-15 concentration had predictive value in predicting CRNM-GIB (AUC 0.8,5%CI: 0.645～0.835, P＜0.001) and all bleeding events (AUC 0.0,5%CI:0.690～0.727, P＜0.001), and ABC bleeding risk score had predictive value in predicting CRNM-GIB (AUC 0.8,5%CI:0.552～0.824, P＜0.001) and all bleeding events (AUC 0.9,5%CI:0.579～0.779, P＜0.001).Compared with the HAS-BLED bleeding risk score, the ABC bleeding risk score had a higher ability to predict cerebral hemorrhage (AUC 0.8,5%CI:0.752～0.985 for ABC score vs. AUC 0.5,5%CI: 0.556～0.933 for HAS-BLED score, net reclassification improvement (NRI) 84.17%, P＝0.001), less ability to predict CRNM-GIB (AUC 0.8,5%CI:0.552～0.824 for ABC score vs. AUC 0.4,5%CI:0.639～0.849 for HAS-BLED score, NRI －23.96%, P＝0.025). Conclusion GDF-15 concentration in blood has predictive value for the bleeding risk of oral NOAC in elderly NVAF patients. Compared with HAS-BLED, ABC bleeding risk score can improve the ability to predict cerebral hemorrhage.

Abstract:Fibrinogen is a plasma protein coagulation factor synthesized in the liver and is associated with coagulation function and inflammation. Coronary heart disease is a disease with high morbidity and mortality in today's society. Previous studies have shown that increased plasma fibrinogen concentration is positively correlated with the morbidity, severity and prognosis of coronary heart disease, which can be used as an independent predictor of coronary heart disease. Further study on the correlation between fibrinogen and coronary heart disease can guide clinical diagnosis and treatment. This article reviews the research progress on the correlation between fibrinogen and coronary heart disease.

Abstract:Atherosclerosis is the basis of many important adverse vascular events, which seriously threatens human health. In recent years, more and more attention has been paid to the role of inflammatory and immune regulatory factors in the occurrence and development of atherosclerosis. It has been noted that the risk of cardiovascular disease in patients with autoimmune diseases is significantly higher than that in ordinary people. It is speculated that there may be a relationship between autoimmune diseases and the pathogenesis of cardiovascular disease cross. Therefore, this paper reviews the mechanism of autoimmune diseases and As by searching the relevant literature at home and abroad, in order to provide new ideas for the prevention and treatment of autoimmune diseases complicated with cardiovascular disease.

Abstract:N6-methyladenine (6mA) is an epigenetic modification existed in eukaryotes, which dynamically regulates transcription by modifying mitochondrial DNA, non-coding genes and ribosomal DNA. Current studies have found that 6mA affects mitochondrial activity and function by regulating mitochondrial DNA transcription, etc., and then participates in the occurrence and development of metabolic diseases. This paper discusses the mechanism of 6mA regulating mitochondrial function and its role in metabolic diseases such as obesity, atherosclerosis, hypertension and cancer, which is expected to provide new ideas for the prevention and treatment of metabolic-related diseases.

Abstract:Atherosclerosis (As) is a key factor in the primary lesions of macrovascular diseases, and dyslipidemia plays a very important role in the process of As. At present, a large number of studies at home and abroad have shown that atherogenic index of plasma (AIP) is closely related to cardiovascular disease, atherosclerosis and other chronic diseases. It is considered that AIP, as a new comprehensive blood lipid index, has predictive value for early cardiovascular risk, metabolic syndrome, chronic kidney disease, immune-related diseases and other common clinical diseases. The purpose of this review is to summarize the clinical research progress of AIP.

Abstract:Succinate is the central metabolite of the mitochondrial tricarboxylic acid cycle and an important metabolite of the intestinal flora. Recent studies have showed that succinate involved in the occurrence, development and outcome of metabolic diseases via “signal molecules”. Obesity, non-alcoholic hepatitis, type 2 diabetes mellitus and metabolic cardiovascular disease are closely related to metabolic homeostasis. This article reviews the relationship between succinate and these four metabolic diseases, and its underlying mechanisms, which might benefit to provide new ideas and strategies for the prevention and treatment of metabolic diseases.