Abstract:Atherosclerosis is the leading cause of cardiovascular and cerebrovascular diseases caused by smoking, hypertension, aging, obesity, circadian clock disorders, and other factors. As a molecular machine for protein synthesis, ribosomes maintain protein homeostasis in cells. This review focuses on the impact of aging, obesity, and circadian clock disorders on the development of atherosclerosis and the relationship with ribosome biogenesis and provides the theoretical basis for both basic research and clinical intervention of atherosclerosis.

Abstract:Aim To investigate the mechanism and signal pathways of xeroderma pigmentosum group D(XPD) gene on the proliferation of human umbilical vein smooth muscle cell (HUVSMC) induced by ox-LDL. Methods HUVSMCs were transfected with the plasmids of pEGFP-N2/XPD using Lipofectamine 2000, and subsequently silent mTOR gene. MTT and EdU assay was used to detect the cell proliferation. Flow cytometry was used to examine the cell apoptosis. The expression of XPD, lectin-like oxidized low-density lipoprotein receptor 1(LOX-1), mTOR, phospho-mTOR, Bcl-2 and Bax was measured by Western blot. Results The expression of XPD and Bax protein was down-regulated in ox-LDL group (P＜0.05), while the expression of LOX-1, mTOR, Bcl-2 protein and the ratio of Bcl-2/Bax was significantly up-regulated (P＜0.05), compared with control group. Cell proliferation of ox-LDL group increased obviously (P＜0.05). After transfected with the pEGFP-N2/XPD plasmid, the expression of Bax was significantly up-regulated, while the expression of LOX-1, mTOR, Bcl-2 and the ratio of Bcl-2/Bax were significantly down-regulated (P＜0.05). Flow cytometry showed that overexpression of XPD increased the apoptosis rate of HUVSMC (P＜0.05). MTT and BdU showed that cell proliferation of pEGFP-N2/XPD group reduced compared with control group (P＜0.05). Compared with control group, the expression of LOX-1 was significantly down-regulated in siRNA mTOR group (P＜0.05). Conclusion XPD can inhibit HUVSMC proliferation and promote its apoptosis, and reduce the effect of ox-LDL promoting proliferation of HUVSMC via the mTOR/LOX-1 pathway. XPD may be the target of treatment of atherosclerosis.

Abstract:Aim To screen the early and advanced atherosclerosis differential genes associated with cuproptosis by bioinformatic methods, and analyze their mechanisms of action, and predict potential biomarkers. Methods The information related to early and advanced atherosclerosis (GSE28829 and GSE43292 data sets) was downloaded from GEO database and standardized. 19 cuproptosis genes were obtained from the literature. Difference analysis, enrichment analysis, consensus clustering algorithm, principal component analysis, immune cell infiltration and screening core genes were used to find their action mechanisms and potential biomarkers. Results Finally, 10 differential genes related to cuproptosis were screened. The correlation analysis of differential genes related to cuproptosis showed a strong positive correlation between GLS and DBT (r＝0.78, P＜0.001), while NLRP3 showed a strong negative correlation with DBT and GLS (r＝－0.62, P＜0.001). GO enrichment analysis of differential genes related to cuproptosis was mainly related to copper ion transport and copper homeostasis, and KEGG analysis showed that it was mainly enriched in platinum resistance, mineral absorption and central carbon metabolic pathway in cancer. The PPI network analysis and MCODE were used to screen core genes. The results of immune cell infiltration showed that M2 macrophages, M0 macrophages, resting CD4 memory T cells, and CD8＋T cells were dominant (P＜0.05). The correlation analysis of differential genes related to immune cells and cuproptosis showed that in the early stage of atherosclerosis, GLS was strongly positively correlated with activated NK cells (r＝0.52, P＜0.001), FDX1 and SLC31A1 was strongestly negatively correlated with CD8＋T cells (r＝－0.51, P＜0.001); in the advanced stage of atherosclerosis, FDX1 was strongestly positively correlated with M0 macrophages (r＝0.58, P＜0.001) and FDX1 was strongestly negatively correlated with CD8＋T cells (r＝－0.55, P＜0.001). Principal component analysis showed that two subtypes C1 and C2 could be clearly distinguished according to the expression of cuproptosis-related differential genes. Conclusion The immune-related changes between cuproptosis and the development of atherosclerosis may be the key to the diagnosis and treatment of early and advanced atherosclerosis, and the core genes SLC31A1, MTF1, ATP7B and ATP7A may be potential markers and therapeutic targets for the development of atherosclerosis.

Abstract:Aim To explore the role of circular RNA spindle and kinetochore-associated protein 3 (circ-SKA3) in regulating Toll-like receptor 4 (TLR4) axis in atherosclerosis (As) through miR-1303. Methods Carotid artery plaque, diseased vascular tissue, normal tissue adjacent to plaque and venous blood were collected from 30 patients with As treated by carotid endarterectomy from April 2019 to April 2022. Another 30 normal venous blood samples were collected. Microarray analysis, quantitative real-time polymerase chain reaction (qRT-PCR) and fluorescence in situ hybridization (FISH) were used to detect the expression and localization of circ-SKA3 in plaque tissue of As patients, control samples, plasma exosome, human umbilical vein endothelial cell (HUVEC) and aorta of As model mice. The relationship among circ-SKA3, miR-1303 and TLR4 was verified by bioinformatics, double luciferase reporter gene detection and RNA immunoprecipitation. The proliferation, migration and angiogenesis of HUVEC were detected by CCK-8, scratch, Transwell and angiogenesis experiments. TLR4 axis-related protein expression was detected by Western blotting. Pathological changes of aorta in As model mice was observed by Oil red O staining, HE staining and Masson staining. TLR4 expression in aorta of As model mice was detected by immunohistochemistry and immunofluorescence. Results The expression levels of circ-SKA3 and TLR4 in plaque tissue, plasma exosome, oxidized low density lipoprotein (ox-LDL) treated HUVEC and circ-SKA3, TLR4 in aortic of As model mice were up-regulated (P＜0.05), while the expression level of miR-1303 was down-regulated (P＜0.05). Functional analysis showed that circ-SKA3 promoted HUVEC damage in vitro and As progress in vivo. Mechanism analysis showed that circ-SKA3 could promote TLR4 expression by adsorbing miR-1303 by sponge. Inhibition of circ-SKA3/miR-1303/TLR4 axis can inhibit the formation of As lesions. Conclusions circ-SKA3 is overexpressed in carotid plaque, plasma exosome, ox-LDL-treated HUVEC and As model mouse aorta in As patients. circ-SKA3/miR-1303/TLR4 axis can promote the development of As model in vivo and in vitro.

Abstract:Aim To explore the correlation between protein tyrosine kinase 7 (PTK7) and coronary heart disease (CHD) and its diagnostic value. Methods Target genes were obtained through the Gene Expression Omnibus (GEO) database. StataSE15 was used to find the total standardized mean difference (SMD) of PTK7 and plot the summary receiver operating characteristic (SROC) curve. Next, reverse transcription quantitative polymerase chain reaction was used to verify the expression of PTK7 in CHD and non-CHD population samples and search for CHD-related single-cell RNA sequencing data from GEO to analyze the expression of PTK7 in different cells. The upstream transcription factor (TF) of PTK7 was predicted by the Cistrome Data Browser database. Moreover, enrichment analysis of the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed on the differentially co-expressed genes. Results By calculating the SMD of PTK7, it was found that PTK7 was highly expressed in the peripheral blood leukocytes (PBL) of patients with CHD (total SMD=0.1,5% confidence interval=0.17~1.45). The population sample validation confirmed the above results. When SROC was plotted, the area under the curve (AUC) was 0.79, indicating that PTK7 has the ability to distinguish between CHD and non-CHD. The single-cell RNA sequencing results showed that the expression ratio of PTK7 was relatively low in different cells of normal peripheral blood. In addition, potential upstream TFs of PTK7 were predicted through the ChIP-seq database, where it was found that IRAK1, SNAI2 may be positive upstream TFs of PTK7, and EP300, NIPBL may be negative upstream TFs of PTK7. Conclusion Highly expressed PTK7 in PBL is positively correlated with the pathogenesis of CHD, demonstrating that PTK7 has definite diagnostic value on CHD.

Abstract:Aim To investigate the correlation between triglyceride-glucose (TyG) index and the severity of coronary artery disease assessed in patients with acute myocardial infarction (AMI). Methods The study restrospectively selected 424 patients with AMI in the Fourth Affiliated Hospital of Xinjiang Medical University from January 2020 to March 2023. Clinical data and results of coronary angiography (CAG) were collected. Gensini score was used to quantitatively assess the degree of coronary artery stenosis. According to tertiles of the Gensini, the patients were classifified into three groups:low Gensini score group (＜45 points, n＝140), medium Gensini score group (45～86 points, n＝143), and high Gensini score group (≥87 points, n＝141). The associations between TyG index and the occurrence of coronary artery disease with high Gensini score by Logistic regression analysis; Spearman correlation was used to analyze the correlation between TyG index and Gensini score in AMI patients; ROC curve was used to analyze the value of TyG index in predicting the severity of coronary artery lesions. Results TyG index of high Gensini score group was significantly higher than that of low and medium Gensini score group (P＜0.05). Logistic regression analysis showed that TyG index was an independent risk factor for severe coronary lesions in AMI patients (OR＝13.7,5%CI:2.642～67.235, P＝0.002). Spearman correlation analysis showed that TyG index was positively correlated with the severity of coronary artery disease (r＝0.331, P＜0.001). ROC curve analysis showed that the area under curve of TyG index was 0.680 (95%CI:0.630～0.731, P＜0.001). When the cut-off value of TyG index was 1.555, the predicted efficacy of of severe coronary artery disease in patients with AMI was the highest, with a sensitivity of 79.4% and a specificity of 50.5%. Conclusion TyG, as a novel biomarker, was significantly and independently associated with the severity of the coronary arteries in patients with AMI.

Abstract:Aim To analyze the incidence and influencing factors of coronary artery calcification (CAC) by low dose chest CT in asymptomatic middle-aged male patients, and to explore the value of low dose chest CT in early screening of cardiovascular diseases. Methods 2 571 asymptomatic male participants aged 40~65 were selected who underwent health examination at General Hospital of Eastern Theater Command from January to December 2022. General data, blood indicators, chest CT and other data were collected, and participants were divided into CAC group (n＝422) and non-CAC group (n＝2 149) according to whether chest CT indicated CAC. The differences between the two groups and the risk factors of CAC were analyzed. Results Among 2 571 asymptomatic middle-aged male patients, the positive rate of CAC was 16.41%. The age, body mass index (BMI), systolic blood pressure, diastolic blood pressure, pulse, waist circumference, alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), triglycerides (TG), fasting blood glucose (FBG), and glycated hemoglobin (HbA1c) were higher in CAC group than in non-CAC group, and the red blood cell count (RBC) was lower in CAC group than that in non-CAC group (all P＜0.05). Univariate Logistic regression analysis showed that the effects of age, BMI, systolic blood pressure, diastolic blood pressure, pulse, waist circumference, RBC, ALT, AST, BUN, TG, FBG, and HbA1c on CAC were statistically significant (all P＜0.05). Multivariate Logistic regression analysis showed that age, BMI, diastolic blood pressure, RBC, and AST were independent risk factors for CAC (all P＜0.05). Conclusion Age, BMI, diastolic blood pressure, RBC, and AST are independent risk factors for CAC in low dose chest CT, and physical examination chest CT is valuable in cardiovascular disease screening.

Abstract:Aim To construct a nomogram model for predicting the risk of coronary artery calcification in patients with chronic obstructive pulmonary disease (COPD) and evaluate its predictive efficiency. Methods The data of DRYAD database were analyzed by the R software. Multivariate Logistic regression analysis was used to screen independent predictors of coronary artery calcification risk in patients with COPD, and a personalized nomogram prediction model was constructed. Receiver operating characteristic (ROC) curve was used to evaluate the predictive effect of the nomogram model. Results Multivariate Logistic regression analysis showed that male, advanced age, use of statins and use of ACE inhibitors or ARB antihypertensive drugs were independent risk factors for coronary artery calcification in COPD patients (P＜0.05). The area under the ROC curve (AUC) of the constructed nomogram model was 0.9,5%CI: 0.725～0.834, suggesting that the nomogram had good discrimination. The Hosmer-Lemeshow goodness-of-fit test showed that there was no significant difference between the predicted probability of nomogram and the actual frequency of coronary artery calcification (χ²＝6.240, P＝0.621), that is, the nomogram model had good calibration. The DCA curve showed that when the threshold probability of coronary artery calcification in COPD patients was between 0.26 and 0.96, the net benefit of patients using the nomogram model was significantly better than that of the “full intervention” and “no intervention” measures, suggesting that the nomogram model has good clinical applicability. Conclusion The nomogram prediction model constructed in this study can be used to assist clinical staff to screen out COPD populations with high risk of coronary calcification, formulate individualized targeted intervention plans, and reduce the incidence of coronary calcification in COPD patients.

Abstract:Cardiopulmonary function is a powerful indicator of overall health and cardiovascular or all-cause mortality. Exercise is an important non-pharmacological treatment modality in the prevention and management of hypertension, primarily including continuous aerobic exercise, high-intensity interval training, and resistance exercise. Different exercise patterns not only contribute to blood pressure reduction in hypertensive patients, but also effectively improve cardiopulmonary function. This article provides a review of the impact of various exercise modalities, particularly aerobic exercise, on the cardiopulmonary function of hypertensive patients, aiming to offer assistance in formulating scientific exercise intervention strategies for individuals with hypertension.

Abstract:Artery stenosis due to atherosclerosis is the most common cause of cardiovascular disease. In addition to known risk factors, researchers have found that intestinal flora can influence the pathogenesis of atherosclerosis through its metabolites (short-chain fatty acids, trimethylamine oxide, indoles), the metabolism of bile acids, and the inflammatory response, and the relevant evidence has been supported experimentally. This article presents a systematic review of the relationship between intestinal flora and atherosclerotic cardiovascular disease, the microscopic mechanisms by which intestinal flora affect the pathogenesis of atherosclerotic cardiovascular disease, and recent advances in the treatment of atherosclerotic cardiovascular disease using intestinal flora as a target.

Abstract:Acute myocardial infarction (AMI) is one of the main causes of death from cardiovascular and cerebrovascular diseases worldwide. Rapid and efficient diagnosis of AMI plays an important role in the treatment and prognosis of the disease. Studies suggest that microRNA (miRNA) may be an important molecular marker for the diagnosis of AMI and provide directions for AMI treatment. This review summarizes the feasibility of miRNA as a diagnostic marker for AMI, its effect on AMI and its related molecular mechanisms.

Abstract:With the deepening understanding of hypertension, more and more evidence suggests that the blood pressure levels of hypertensive patients are closely related to sodium salts. The gut microbiome is made up of bacteria, archaea, fungi, protozoa and viruses, also known as the gut microbiome, intestinal flora and its metabolites, as a hot research direction in hypertension, play an important role in the relationship between sodium and blood pressure. Excessive sodium salt can change the type and proportion of intestinal microbiota, affect the level of inflammation and metabolism of the body and accelerate the occurrence and development of hypertension. Sodium control is a low-cost and effective way to control blood pressure. This article reviews the complex relationship between sodium salts, gut microbiota, and hypertension, hoping to provide theoretical support for the prevention, treatment, and control of hypertension.