Abstract:

Atherosclerosis is a chronic vascular disease primarily affecting large and medium-sized arteries, involving multiple complex pathogenic factors. In recent years, numerous research trends in atherosclerosis, such as inflammation, gut microbiota, pyroptosis, ferroptosis, autophagy, cuproptosis, exosome and non-coding RNA have emerged.This article aims to review the recent advancements in these research directions, with the hope of opening new avenues for the mechanism of atherosclerosis and the treatment of diseases related to atherosclerosis.

Abstract:

In the study of cardiovascular diseases, Peroxiredoxin 6 (PRDX6) is the only mammalian 1-Cys member of the Peroxiredoxin (PRDX) family and has attracted much attention. PRDX6 plays a unique role in oxidative stress due to its peroxidase activity and phospholipase A2 activity, and has been shown to participate in redox homeostasis and phospholipid metabolism. In recent years, the role of PRDX6 in the occurrence and development of cardiovascular diseases has received great attention. However, there is no unified understanding of the function of PRDX6 in the cardiovascular system at present. This article aims to briefly summarize the research progress of PRDX6 in cardiovascular diseases such as atherosclerosis, pulmonary hypertension, myocardial infarction, heart failure, abdominal aortic aneurysm, and systematically review the expression changes, mechanism of action, and possible therapeutic potential of PRDX6 in these cardiovascular diseases, hoping to provide new ideas and strategies for cardiovascular diseases intervention.

Abstract:

Aim To study the effect of maternal high-fat diet during pregnancy on endothelial to mesenchymal transition of aortic vessels in adult offspring. Methods The pregnant mice were randomly divided into normal diet group and high-fat diet group, and the offspring mice were fed normally for 16 weeks after the mother gave birth. Western blot and RT-qPCR were used to detect the expression and transcription of related proteins, and immunofluorescence and immunohistochemical staining were used for pathological analysis. Results Compared with the offspring of maternal normal diet during pregnancy, the expressions of vascular inflammatory factors, macrophage infiltration, monocyte-endothelium adhesion were significantly increased in the offspring of maternal high-fat diet (OHF) during pregnancy (P＜0.05). Vascular endothelial nitric oxide synthase (eNOS) activity, nitric oxide (NO) level were dramatically reduced (P＜0.05). Immunofluorescence results showed reduced endothelial cell marker CD31 and increased mesenchymal marker α-smooth muscle actin (α-SMA) in OHF. Western blot analysis further confirmed the results, which showed that maternal high fat diet reduced vascular endothelial-cadherin (VE-cadherin) and CD31 and increased α-SMA and Vimentin in the offspring (P＜0.05). The maternal high fat diet increased the extracellular matrix protein disposition and transforming growth factor beta (TGF-β)/Smad signaling in endothelium (P＜0.05). Moreover, the maternal high fat diet reduced Kruppel-like factor 2 (KLF2)expression by 76% in mRNA level and 59% in protein level (P＜0.05). Conclusion Maternal high-fat diet during pregnancy lead to a transition of endothelial to mesenchyme in the offspring aorta. The results provide a clue for prevention of vascular disease in early stage.

Abstract:

Aim The effect of miR-223-3p on H9c2 cells in high glucose environments was investigated through bioinformatics and its role in the mechanism of development of diabetic cardiomyopathy was analyzed in conjunction with transcriptomic sequencing results. The objective was to identify novel therapeutic targets at the molecular level and explore the specific mechanisms of action of miR-223-3p. Methods In high glucose-cultivated H9c2 cells, miR-223-3p inhibition and control were transfected, respectively. RT-qPCR was used to detect the differences in miR-222-3p expression between the two cell groups. Differential mRNA was identified through high-throughput sequencing. GO functional analysis was conducted using TopGO software. DESeq2 software (v1.16.1) filtered differentially expressed genes and analyzed them using a miR-223-3p target gene database. This process predicted the target genes of miR-223-3p and validated the changes in their expression through RT-qPCR. Results The activity of H9c2 cells treated with high glucose decreased significantly. Significant differences in gene expression between the control group and the inhibitor group had been indicated by transcriptomic sequencing results. GO function enrichment analysis showed that the predicted target gene set was significantly enriched in G protein-coupled receptor activity, glycerol ether monooxygenase activity, cellular anion homeostasis, and chloride ion homeostasis, among others. KEGG pathway enrichment analysis further showed that these genes were mainly involved in the TNF signaling pathway and the IL-17 signaling pathway. In addition, they were related to type 1 diabetes, cytochrome P450 metabolism of exogenous drugs, and other diseases and physiological processes. Target gene prediction suggested that miR-223-3p may be associated with the expression changes of Cxcl10, Creb3l3, Mmp3, and Bcl3, among others. Conclusion The prediction of miR-223-3p and its downstream target genes in high glucose induced H9c2 cell injury may provide new targets for the treatment of diabetic cardiomyopathy, which is of great significance for revealing the pathogenesis of diabetic cardiomyopathy and developing new treatment strategies.

Abstract:

Aim To investigate the protective effect of remimazolam (Re) combined with thoracic sympathetic nerve block (TSNB) on myocardial ischemia/reperfusion (MI/R) rats. Methods Rats were randomly separated into control group, MI/R group, Re group, TSNB group, and Re+TSNB group, with 12 rats in each group. Except for the control group, the remaining rats were subjected to left anterior descending coronary artery (LAD) ligation to construct an MI/R model. In the Re group, 20 mg/kg Re was intraperitoneally injected 30 min before ischemia. In TSNB group, 0.2% ropivacaine 50 μL was injected into the thoracic epidural catheter 30 min before ischemia. In the Re+TSNB group, 20 mg/kg Re was intraperitoneally injected and 0.2% ropivacaine 50 μL was injected into the thoracic epidural catheter 30 min before ischemia. The control group and MI/R group were injected with normal saline only. Rats in each group were evaluated for cardiac function and infarct size. HE staining and TUNEL staining were applied to observe pathological changes in myocardial tissue and myocardial cell apoptosis. Serum myocardial injury markers creatine kinase (CK) and aspartate transaminase(AST), cardiac troponin(cTnI), myocardial inflammatory factors interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α), and oxidative stress factors malondialdehyde (MDA), superoxide dismutase (SOD) were detected. Western blot was applied to detect the expression of IL-8, TNF-α,Bü lymphoblastoma-2-associated X protein(Bax), and B-lymphoblastoma-2 (Bcl-2) in myocardial tissue. Results Compared with the control group, the myocardial cells of rats showed edema and myocardial fiber disorder in the MI/R group, the left ventricular developmental pressure(LVDP), maximal left ventricular pressure rising rate(+dp/dt_max),maximal left ventricular pressure decreasing rate (－dp/dt_max), SOD activity, and level of Bcl-2 were significantly reduced, the myocardial infarction area, cell apoptosis rate, levels of cTnI, CK, AST, IL-8, TNF-α, MDA, and Bax were increased (P＜0.05). Compared with the MI/R group, the morphology of myocardial fibers and myocardial cells was significantly improved in the Re group, TSNB group and Re+TSNB group, the LVDP, ±dp/dt_max, SOD activity, and level of Bcl-2 were significantly increased, the myocardial infarction area, cell apoptosis rate, levels of cTnI, CK, AST, IL-8, TNF-α, MDA, and Bax were significantly decreased (P＜0.05). Compared with the Re group and TSNB group, the LVDP, ±dp/dt_max, SOD activity, and level of Bcl-2 were significantly increased in the Re+TSNB group, the myocardial infarction area, cell apoptosis rate, levels of cTnI, CK, AST, IL-8, TNF-α, MDA, and Bax were significantly decreased (all P＜0.05). Conclusion The combination of Re and TSNB may protect against MI/R injury by reducing myocardial infarction and myocardial cell apoptosis, and inhibiting inflammatory response and oxidative stress.

Abstract:

Aim To investigate the correlation between serum remnant lipoprotein cholesterol(RLP-C), triglyceride levels(TG) and coronary heart disease(CHD) in middle-aged people. Methods A total of 439 middle-aged individuals who were hospitalized in the Department of Cardiology of Liuzhou People's Hospital from January 2015 to December 2022 and underwent coronary angiography were selected as the research subjects. They were divided into CHD group (190 cases) and control group (249 cases) according to the results of coronary angiography. The general clinical data and laboratory tests of the subjects were collected,and RLP-C was calculated based on blood lipid profile. Bivariate Spearman correlation, multivariate Logistic regression, and restricted cubic spline graph were used to analyze the correlation between RLP-C, TG, and CHD in these middle-aged participants. Receiver operating characteristic (ROC) curve was used to evaluate the value of RLP-C and TG in predicting CHD. Results The age in CHD group was older than that in control group, proportion of male, proportion of smoking history, incidence of hypertension, incidence of diabetes, incidence of hyperlipidemia, body mass index (BMI), systolic blood pressure(SBP), fasting blood glucose (FBG), glycosylated hemoglobin (HbA1c), TG, low density lipoprotein cholesterol (LDLC), RLP-C were higher than those in control group, while high density lipoprotein cholesterol (HDLC) was lower than that in control group (P＜0.05). The Spearman correlation analysis results showed positive correlation between RLP-C, TG, LDLC and CHD (r＝0.7,0.279, and 0.105, respectively, P＜0.05), and negative correlation between HDLC and CHD (r＝－0.340, P＜0.001) in these studied population. Multivariate Logistic regression analysis showed that whether as continuous or categorical variables, RLP-C and TG were independent risk factors for CHD (P＜0.05), HDLC was independent protective factor for CHD (P＜0.05). Compared with lowest quartile group, The OR (95%CI) of CHD incidence in 3rd and 4th quartile group of RLP-C were 2.648(1.364~5.144) and 2.847(1.468~5.520) respectively; The OR (95%CI) of CHD incidence in 3rd and 4th quartile group of TG were 3.043(1.520~6.092) and 3.520(1.811~6.842) respectively. The restricted cubic spline graph revealed that RLP-C, TG were positively nonlinearly correlated with CHD (P for overall＜0.001, P for nonlinear＝0.2,0.001, respectively). Subgroup analysis showed that the relationship between RLP-C, TG and CHD was more significant in females than in males. ROC curve analysis showed that the areas under the curve (95%CI) of RLP-C, TG in predicting CHD were 0.632(0.580~0.685) (P＜0.001) and 0.663(0.612~0.713) (P＜0.001) in general, meanwhile, 0.735(0.659~0.811) (P＜0.001) and 0.740(0.666~0.813) (P＜0.001) in females. Conclusion RLP-C and TG are independent risk factors for CHD in middle-aged people, and their correlation with CHD are greater than that of LDLC. They may become the main targets for the prevention and treatment of CHD, and should be given clinical attention.

Abstract:

Aim To develop and validate a dynamic nomogram to predict the risk of no-reflow phenomenon (NRP) after percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI) by constructing HALP based on haemoglobin (Hb), albumin (Alb), lymphocytes (LYM), and platelets (PLT). Methods A retrospective analysis of 449 STEMI patients admitted to Nanyang Central Hospital from January 2022 to January 2024 was divided into 145 cases in the NRP group and 304 cases in the normal reflow group according to whether the patients developed NRP after surgery. HALP was calculated based on Hb, Alb, LYM and PLT observations. Independent influences on NRP risk were determined by multivariate Logistic regression analysis. Dynamic nomogram of NRP risk after PCI in STEMI patients were developed using the R language correlation software package. Results The incidence of NRP was 32.3% (145/449) among 449 patients with NRP. The HALP of patients in the NRP group was lower than that of patients in the normal reflow group (P＜0.05). The area under the curve (AUC) of HALP for diagnosis of NRP was 0.880 (0.847～0.909), and the Kappa coefficient of its optimal cutoff value ≤3.04 versus patients with accurate diagnosis of NRP was 0.612. The results of multivariate Logistic regression analysis showed that age, diabetes mellitus, and high sensitivity C-reactive protein (hs-CRP) were independent risk factors for NRP after PCI in STEMI patients (P＜0.05), and left ventricular ejection fraction (LVEF) and HALP were independent protective factors (P＜0.05). A dynamic nomogram (https://xz0311.shinyapps.io/DynNamicNRP/) based on HALP combined with age, diabetes, LVEF, and hs-CRP was effective in predicting the risk of post-PCI NRP in STEMI patients. Conclusion HALP is more effective than traditional risk factors in predicting NRP risk in STEMI patients after PCI, and the dynamic nomogram developed based on HALP will help develop personalized treatment strategies for patients with high NRP risk.

Abstract:

Aim To explore the correlation between carotid atherosclerosis (CAS) and neutrophil/lymphocyte ratio (NLR) in patients with early morning hypertension, and to construct a line chart model to predict the risk of CAS in patients with hypertension in the morning. Methods 255 patients with early morning hypertension hospitalized in the Affiliated Hospital of Chengde Medical College from October 2019 to November 2022 were collected, and their basic data, blood routine and blood biochemical indexes were collected. All selected patients need to improve 24-hour ambulatory blood pressure monitoring and carotid artery color ultrasound detection. According to the presence or absence of CAS, all selected patients were divided into morning hypertension with CAS group (n＝197) and morning hypertension without CAS group (n＝58). Multivariate Logistic regression analysis was used to explore the risk factors of early morning hypertension with CAS, and to construct and verify an individual line chart model to predict the risk of early morning hypertension patients with CAS. Results The age, NLR, neutrophils (NE), monocytes (MO), white blood cell (WBC), total cholesterol (TC), triglyceride (TG) and low density lipoprotein cholesterol (LDLC) increased in the early morning hypertension with CAS group compared with those in the morning hypertension group without CAS, while the HDLC decreased(P＜0.05). The results of multivariate Logistic regression analysis showed that the age, NLR and TC were higher in the early morning hypertension with CAS group than those in the early morning hypertension without CAS group, while HDLC was lower; Age, NLR and TC were independent risk factors of early morning hypertension with CAS, while HDLC was independent protective factors of morning hypertension with CAS. Based on the results of multivariate Logistic regression analysis, an individualized line chart model for predicting early morning hypertension with CAS was constructed. The area under the ROC curve of the line chart model was 0.853 (95%CI:0.802～0.904, P＜0.01). The result of Hosmer Lemeshow fit test was χ²=1.665 (P＞0.05). Conclusions There was a positive correlation between NLR and morning hypertension with CAS, and NLR was an independent risk factor for morning hypertension with CAS. The individualized line chart model based on age, NLR, TC and HDLC can effectively predict the risk of hypertension with CAS in the early morning, which provides a theoretical basis for early detection and prevention of atherosclerosis.

Abstract:

Aim To construct a diabetic atherosclerosis mouse model and study the pathological characteristics of diabetic atherosclerosis. Methods Fifty 8-week-old male LDLR－/－ mice were fed with standard diet for 2 weeks and then changed to high-fat diet, they were randomly divided into two groups. The diabetic atherosclerosis group was given intraperitoneal injection of low dose streptozotocin (STZ) for 5 days continuouly to establish the model, and the atherosclerosis group was given citrate buffer injection at the same time. The body mass, blood glucose and blood lipids of the mice in the two groups were detected for many times. At the age of 23 weeks, the mice were euthanized after glucose tolerance test. HE staining and oil red O staining were used to detect the gross and aortic root atherosclerosis, immunohistochemical staining was used to detect CD4, α-smooth muscle actin (α-SMA), EGF-like module-containing mucin-like hormone receptor-like 1 (EMR1), monocyte chemotactic protein-1 (MCP-1), NOD-like receptor protein 3 (NLRP3), vascular cell adhesion molecule-1 (VCAM-1), matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinase-1 (TIMP-1), Western blot was used to detect α-SMA, CD4, tumor necrosis factor-α (TNF-α), NLPR3, intercellular adhesion molecule-1 (ICAM-1), and type Ⅰ and Ⅲ collagen.Results Compared with the atherosclerosis group, the body mass decreased, the levels of total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDLC) increased, and the levels of high density lipoprotein cholesterol (HDLC) decreased (P＜0.05) in the diabetic atherosclerosis group. Compared with the atherosclerosis group, the distribution of atherosclerotic plaques was diffuse and the area was increased in the diabetic atherosclerosis group, and the contents of lipids,Tü cells, macrophages, smooth muscle cells, type Ⅰ and Ⅲ collagen were increased (P＜0.05); the protein levels of TNF-α, MCP-1, MMP-2, NLRP3, ICAM-1 and VCAM-1 in vascular tissues were increased, while the content of TIMP-1 were decreased and MMP2/TIMP-1 were increased (P＜0.05). Conclusions LDLR－/－ mouse model of diabetic atherosclerosis can be successfully established by STZ induction combined with high-fat diet, which can reflect the plaque composition and inflammatory characteristics of diabetes promoting atherosclerosis. It can be used as a relatively ideal pathological model for the study of diabetic macroangiopathy.

Abstract:

Atherosclerosis is the most common disease in cardiovascular and cerebrovascular diseases, and vascular endothelial dysfunction is the initial stage of atherosclerosis. As a physical barrier between the flowing blood and the endothelium,glycocalyx can participate in the occurrence and development of atherosclerosis by regulating vascular permeability, diastolic function, intercellular communication and inflammatory cell adhesion. Therefore, the maintenance or restoration of the integrity of the glycocalyx may be a potential therapeutic target for atherosclerosis. Moreover, the abscission level of glycocalyx can reflect the severity of atherosclerosis. Therefore, the level of glycocalyx degradation products (such as acetheparan sulfate, hyaluronic acid, etc) may be used to evaluate the severity of atherosclerosis in the future. This review summarizes the research progress of glycocalyx in atherogenesis.

Abstract:

The regulatory role of pericoronary adipose tissue (PCAT) in cardiovascular diseases is of paramount importance. PCAT exerts extensive pathophysiological effects on the cardiovascular system by secreting various bioactive substances, such as adipokines and cytokines. Currently, the attenuation value of PCAT can be detected via coronary computed tomography angiography (CCTA), a method that not only reflects the level of vascular inflammation but also holds significant clinical value in the detection and prognostic assessment of coronary heart disease plaques. Therefore, this article reviews the pathophysiological mechanisms of PCAT and its clinical significance in coronary heart disease.

Abstract:

Patients with metabolic syndrome (MS) are at potential risk for cardiovascular disease and have received increasing public and medical attention. Studies have shown that regular physical exercise can effectively regulate metabolic indicators such as blood pressure, blood sugar and blood lipids, and play a positive role in reducing the risk of cardiovascular disease and improving the prognosis of patients. Exercise intensity has been identified as the most important aspect in reducing the risk of cardiovascular death and all-cause mortality in exercise intervention. Therefore, the design of exercise prescription which is both scientific and satisfying individual differences has become the focus of research. Most of the current clinical studies are based on the percentage of exercise intensity as the basis for the formulation of standardized exercise prescription for MS patients, while the studies on the individualized threshold of exercise intensity based on cardiopulmonary exercise test (CPET) are still few. CPET has shown that individualized exercise prescription can effectively reduce body composition index, blood pressure and blood glucose, improve cardiorespiratory function, exercise endurance and quality of life in MS patients. This paper reviewed the development of individualized exercise programs with different intensification according to threshold indexes in CPET, analyzed the intervention effects and possible mechanisms for MS patients and subgroups, and provided certain reference for the formulation and implementation of personalized exercise prescriptions for MS patients, and also provided references for in-depth research on individualized exercise intervention for MS.