Abstract:Atherosclerosis is recognized as an inflammatory disease, and its development is regulated by multiple factors, particularly dyslipidemia. Peroxisome proliferator-activated receptor (PPAR) regulate the expression of genes that are involved in lipid metabolism and inflammation; and they have three subfamily members including PPARα, PPARβ, and PPARγ. However, synthetic PPAR agonists exhibit ambiguous effects in atherosclerotic therapy and induce various side effects. Notably, recent studies demonstrate that traditional Chinese medicine (TCM) alleviate atherosclerotic cardiovascular diseases via suppressing hyperlipidemia and inflammation through regulation of PPAR signaling pathway. This article primarily reviews the regulatory effects of TCM on PPAR and their therapeutic effects on atherosclerosis, provides valuable information for pharmacologists that are interested in searching for effective herbal prescriptions for atherosclerosis therapy and for clinicians that are interested in prevention and treatment of atherosclerotic cardiovascular diseases using TCM.

Abstract:Cardiovascular diseases (CVD) are common complex diseases caused by the interaction of genetic and environmental factors and are closely related to epigenetic modifications. Recent studies have found that lactylation modification, a newly discovered epigenetic mechanism, regulates histones by adding lactyl groups to lysine residues, thereby promoting the transcription and expression of specific genes. Moreover, it also affects the structure and function of non-histone proteins and plays important roles in the pathogenesis of CVD such as atherosclerosis (As), myocardial infarction (MI), ischemia reperfusion injury (IRI)and heart failure (HF) by regulating protein function and gene expression. In this review, the author summarizes and elaborates on the relevant literature on the roles of lactylation modification in CVD published in recent years, in order to provide reference for future research.

Abstract:Aim To explore the potential mechanism of metformin on ATP-binding cassette transport A1 (ABCA1) expression. Methods J774A.1 macrophages were treated with metformin and cycloheximide, and ABCA1 expression was determined by Western blot. His-tagged ABCA1 and HA-tagged Ub plasmids were co-transferred into HEK293 cells and stimulated with metformin. Co-immunoprecipitation (Co-IP) was used to test the binding ability of ABCA1 and ubiquitin. Candidate E3 ubiquitin-protein ligases (CE3) of ABCA1 were identified through Co-IP-based proteomics. The MIB1 plasmid was constructed and transferred into HEK293 cells, and Western blot was used to determine the effect of metformin and MIB1 on ABCA1 expression. Results Metformin increased the expression of ABCA1 in J774A.1 cells (P＜0.01), and inhibited ABCA1 degradation (P＜0.05). Metformin disrupted the binding of ABCA1 to ubiquitin (P＜0.05). The proteins regulated by metformin in ABCA1 expression were primarily enriched in pathways related to cell development, inflammation and immune defense. Metformin may upregulate ABCA1 protein expression via MIB1 (P＜0.05). Conclusion Metformin inhibits the degradation of ABCA1 by blocking the ubiquitin-proteasome system (UPS), and MIB1 might act as a candidate E3 ubiquitin-protein ligase (CE3) for ABCA1.

Abstract:Aim To investigates whether sphingosine-1-phosphate (S1P) regulates the expression of mitochondrial calcium uniporter (MCU) via the sphingosine-1-phosphate receptor/proline-rich tyrosine kinase 2 (S1PR/Pyk2) signaling pathway, thereby reducing oxidative stress-induced mitochondrial damage and inhibiting mitochondria-related apoptosis. Methods Human umbilical vein endothelial cells (HUVEC) were subjected to oxidative damage using hydrogen peroxide (H₂O₂) as a model. Different concentrations of S1P were applied to the oxidative damaged HUVEC. Additionally, the S1PR1 agonist SEW2871, the S1PR1 inhibitor W146, and the Pyk2 inhibitor PF-562271 were used to explore the specific mechanism of S1P action. Results S1P treatment significantly alleviated oxidative damage in HUVEC and was accompanied by an increase in S1PR1 expression (P＜0.05), while S1PR3 expression remained unchanged. Meanwhile, the expression levels of Pyk2 and MCU decreased (P＜0.05). SEW2871 further reduced mitochondrial damage, whereas W146 exacerbated it (P＜0.05). Furthermore, the application of the Pyk2 inhibitor PF-562271 also reduced H₂O₂-induced mitochondrial damage (P＜0.05), further confirming the role of Pyk2 in this process. Conclusion S1P reduces H₂O₂-induced mitochondrial damage and inhibits mitochondria-related apoptosis in HUVEC by suppressing Pyk2 expression via S1PR1.

Abstract:Aim To explore the effect of Nf1 gene silencing on smooth muscle cell proliferation and migration and its possible molecular mechanism. Methods Using mouse aortic vascular smooth muscle cells (MOVAS) as the research object, the efficiency of Nf1 siRNA transfection in MOVAS was verified by RT-qPCR after transfection with Nf1 siRNA. The experiment was divided into control group, siRNA NC group, and Nf1 siRNA group. Ki-67 immunofluorescence assay was used to detect the proliferation of MOVAS. Scratch assay and Transwell assay were used to evaluate the effect in the migration ability of MOVAS caused by Nf1 gene silencing. Western blot was used to detect the effect of Nf1 gene silencing on the expression levels of MOVAS phenotype marker proteins and the differences in the expression levels of downstream Ras signals extracellular signal-regulated kinase (ERK), p-ERK, protein kinase B (Akt), and p-Akt. Results Compared with the control group, the proliferation ability of MOVAS in the Nf1 siRNA group was significantly increased (increased by 33.23%, P＜0.05), migration ability was significantly enhanced (scratch assay showed an increase of 35.47%, Transwell assay showed an increase of 39.33%, P＜0.05 or P＜0.01), and the expression of contractile proteins smooth muscle 22α (SM22α), α-smooth muscle actin (α-SMA), and calmodulin 1 (CNN1) was reduced (decreased by 18.91%, 23.38% and 25.08%, P＜0.05 or P＜0.01, respectively). The expression of synthetic protein osteopontin (OPN) was increased (increased by 58.70%, P＜0.05), and the levels of p-ERK and p-Akt were significantly increased (increased by 33.30% and 2.42 times, respectively, P＜0.05 or P＜0.01). Conclusion Nf1 gene silencing can significantly enhance the proliferation and migration ability of MOVAS, and transform from a contractile phenotype to a synthetic phenotype.

Abstract:Aim To explore the effect of ultrasound-treated polystyrene nanoplastics (PS-NP) on lipid accumulation in macrophage-derived foam cells. Methods The CCK-8 method was used to detect the effects of PS-NP and high-frequency ultrasound-treated PS-NP (UPS-NP) on the activity of macrophages, oil red O staining and cholesterol detection kit were used to detect the intracellular lipid accumulation, RT-qPCR and Western blot were used to detect the expression of mRNA and protein related to cholesterol uptake and efflux, as well as mRNA levels of cell burial related receptors. Results UPS-NP had no significant effect on the activity of macrophages, but UPS-NP could significantly increase the formation of macrophage-derived foam cells and increase the lipid accumulation in foam cells. UPS-NP could significantly upregulate the mRNA and protein expression of CD36 and scavenger receptor-A1 (SR-A1), but did not affect the mRNA and protein expression of cholesterol efflux related receptors ATP-binding cassette transporter A1 (ABCA1) and scavenger receptor-B1 (SR-B1). UPS-NP did not affect the mRNA levels of receptors related to cell burial processes. Conclusion Ultrasound-treated PS-NP can significantly increase lipid accumulation in macrophage-derived foam cells, and its mechanism is related to the upregulation of CD36 and SR-A1 expression.

Abstract:Aim To systematically analyze the risk factors for comorbid ischemic cardiovascular and cerebrovascular diseases using principal component analysis. It seeks to identify key risk factors influencing comorbidity and to construct a predictive model to serve as a screening tool for the prevention and management of comorbidities. Methods This retrospective study included patients diagnosed with coronary artery disease from December 1,9 to June 0,0, at the First Affiliated Hospital of Xinjiang Medical University, using data from the hospital's integrated coronary heart disease prevention platform. Patients were divided into two groups:those with both cardiovascular and cerebrovascular diseases and those with only coronary artery disease based on inclusion and exclusion criteria. Clinical indicators during hospital admission were collected. The sample was randomly divided into a modeling set and a validation set in a 7∶3 ratio. In the modeling set, principal component analysis was used to explore the distribution differences in risk factors between the comorbid group and the single-disease group. By analyzing factor load contributions, the most significant variables were identified. Logistic regression was then used to construct a predictive model, and a nomogram was generated. The model's predictive ability and robustness were evaluated in the validation set. Results A total of 11 808 participants were included, with 2 781 (23.6%) in the comorbid group and 9 027 (76.4%) in the coronary heart disease-only group. Compared with the single-disease group, the comorbid group had a higher average age, a greater proportion of females, and higher systolic blood pressure levels at admission (P＜0.001). Additionally, the levels of hemoglobin, platelet distribution width, low density lipoprotein, and blood sodium were significantly higher in the comorbid group (P＜0.05). A total of 8 265 participants were randomly assigned to the modeling set. Principal component analysis identified seven key factors with factor load contributions greater than 5:sodium level, systolic blood pressure, diastolic blood pressure, age, hemoglobin concentration, platelet distribution width, and total bilirubin level. Using these factors, a nomogram was constructed via Logistic regression. The nomogram's area under the receiver operating characteristic curve for predicting comorbid ischemic cardiovascular and cerebrovascular diseases was 0.630(95%CI:0.600~0.768, P＜0.001). A total of 3 543 participants were randomly assigned to the validation set. In the validation set, the receiver operating characteristic curve was 0.628. Conclusion Elevated sodium level, higher systolic and diastolic blood pressure at admission, older age, increased hemoglobin concentration, higher platelet distribution width, and lower total bilirubin level are risk factors for comorbid ischemic cardiovascular and cerebrovascular diseases. The nomogram constructed has clinical value for screening patients with such comorbidities.

Abstract:Aim To investigate the correlation between the new version of the European System for Cardiac Operative Risk Evaluation Ⅱ (EuroSCORE Ⅱ) score, Gensini score and the occurrence of major adverse cardiovascular events (MACE) after percutaneous coronary intervention (PCI) in patients with coronary heart disease (CHD). Methods A total of 203 CHD patients undergoing PCI treatment admitted to the Department of Cardiovascular Surgery of the First Affiliated Hospital of Air Force Military Medical University from January 2021 to March 2023 were selected as the study objects. Depending on whether MACE happened or not, they were divided into MACE group and non-MACE group.The clinical data of the two groups of patients was compared. Pearson's correlation coefficient was used to analyze the correlation between EuroSCORE Ⅱ score and Gensini score; Logistic regression model was used to evaluate the risk factors for the development of MACE after PCI in patients with CHD; and ROC curves was used to analyze the predictive value of predictive indexes for the development of MACE after PCI in patients with CHD. Results In 203 cases of CHD patients who underwent PCI, 65 of them experienced MACE during the 1-year postoperative follow-up (32.02%). The age, rate of history of diabetes mellitus, rate of Killip classification ≥ gradeⅡ, rate of ≥ 2 diseased vessels, rate of ≥ 2 stents, EuroSCOREⅡscore, and Gensini score of the MACE group were higher than those of the non-MACE group, and the differences were all statistically significant (P＜0.05). The results of the Pearson's correlation analysis indicated that there was a positive correlation between the EuroSCOREⅡscore and Gensini score (r＝0.200, P＝0.004). Logistic regression model analysis showed that age increase, Killip classification ≥ gradeⅡ, high EuroSCOREⅡscore, and high Gensini score were independent risk factors for the development of MACE after PCI in CHD patients (P＜0.05). ROC curve analysis showed that age increase, Killip classification ≥ gradeⅡ, EuroSCOREⅡscore, Gensini score, and combined prediction had statistical significance in determining the occurrence of MACE after PCI (P＜0.05); The area under the curve (AUC) of combined prediction was 0.3,5%CI was 0.928~0.979, sensitivity was 0.892, specificity was 0.891, indicating high predictive value. Conclusion Age increase, Killip classification≥gradeⅡ, high EuroSCOREⅡscore, and high Gensini score are independent risk factors for the occurrence of MACE after PCI in patients with CHD, and all of them have a certain predictive value for MACE after PCI in patients with CHD, and the combined predictive value is higher.

Abstract:Aim To investigate the predictive value of the Murray law-based quantitative flow ratio (μQFR) after target vessel pretreatment for vascular-related adverse events in patients with de novo coronary lesions treated with drug-coated balloon. Methods This retrospective study included 223 lesions from 223 patients who underwent drug-coated balloon-only strategy and completed 2-year clinical follow-up. Coronary angiographic images of target vessels pre-procedure, post-balloon and post-procedure were collected, and analyzed using a novel Murray's law-based algorithm. The μQFR analysis of each target vessel included not only the μQFR value of the target vessel, but also the length of the target vessel, the degree of vessel diameter stenosis, the reference lumen diameter, the minimum lumen diameter and blood flow velocity. The primary endpoint was defined as the postoperative vessel-oriented composite endpoint (VOCE). Results During the 2-year clinical follow-up period, a total of 25 patients (11.2%) experienced VOCE events. Compared with the control group, patients with VOCE events after pretreatment showed a decrease in μQFR (P＜0.001). Multivariate Logistic analysis showed that a lower target vessel μQFR after pretreatment (OR＝0.1,5%CI:0.894～0.969, P＜0.001) was an independent predictor of VOCE events. ROC curve analysis showed that the cut-off value for predicting 2-year VOCE events using preprocessed μQFR was 0.83 (95%CI:0.727～0.840), with a sensitivity of 72.7% and a specificity of 84.0% (AUC＝0.3,5%CI:0.676～0.870, P＜0.001). Survival analysis showed that compared with patients with μQFR＞0.83, patients with μQFR≤0.83 had a significantly higher incidence of VOCE events at 1 and 2 years, increasing to 3.909 times (16.9% vs. 4.6%, HR＝3.9,5%CI:1.539～9.930, P＝0.004) and 2.867 times (19.7% vs. 7.2%, HR＝2.7,5%CI:1.301～6.316, P＝0.009). After adjusting for potential confounds, patients with pretreated μQFR≤ 0.83 had a 2.567 times in 2-year incidence of VOCE events (HR＝2.7,5%CI:1.151～5.727, P＝0.021) and a 3.712 times in 1-year incidence of VOCE events (HR＝3.2,5%CI:1.478～9.810, P＝0.006) compared to patients with good pretreatment. Conclusions For patients with in situ coronary artery disease, a lower μQFR after pretreatment increases the risk of postoperative adverse clinical events. μQFR≤0.83 may be used to evaluate the effectiveness of lesion pretreatment.

Abstract:Cardiovascular disease is an important problem affecting global human health, and its incidence is increasing year by year. In recent years, more and more studies have shown that sex-determined region of Y (SRY)-related high mobility group-box 9 (SOX9) gene, as a highly conserved transcription factor, is widely involved in regulating cardiac dvelopment and cardiovascular disease progression at the level of gene transcription. SOX9, alone or in combination with other proteins, can bind to corresponding cis-acting elements in the downstream target gene promoter region and participate in regulating the expression of downstream heart development or cardiovascular disease-related genes. Therefore, SOX9 has the potential to be a new therapeutic target for the cardiovascular system. In this paper, the structure and function of SOX9 were systematically described, and the latest research progress of SOX9 in cardiac remodeling and vascular remodeling was summarized, in order to provide new ideas and methods for the prevention and treatment of cardiovascular system diseases in the future.

Abstract:To analyse the role and mechanism of lipid metabolism disorder in vascular aging caused by endothelial cells, smooth muscle cells, and macrophages. Lipid metabolism disorder damages endothelial cells and promotes vascular aging through the reactive oxygen species (ROS) pathway, endothelial nitric oxide synthase (eNOS) activity, oxidized low density lipoprotein (ox-LDL), inflammasomes, and various inflammatory factors. Lipid metabolism disorder accelerates vascular aging process through autophagy, DNA damage, and nuclear factor-κB (NF-κB) in vascular smooth muscle cells.Lipid metabolism disorder stimulates macrophages in the vascular wall to secrete various inflammatory factors that act on the Toll-like receptor (TLR) pathway, promoting oxidative stress and causing DNA damage, thereby promoting vascular aging.Lipid metabolism disorder promotes oxidative stress and chronic inflammation in endothelial cells, smooth muscle cells, and macrophages, leading to vascular aging.

Abstract:Pyroptosis is a form of programmed cell death characterized by prominent inflammatory responses. As a classic chronic inflammatory disease, atherosclerosis (As) has been demonstrated to exhibit specific expression of multiple pyroptosis-related proteins within plaques. Accumulating evidence indicates that pyroptosis plays a crucial regulatory role in the initiation and progression of As. This review primarily focuses on three key cell types involved in As—endothelial cell, macrophage, and vascular smooth muscle cell (VSMC), and systematically summarizes their pyroptotic mechanisms and contributions to atherosclerotic development. Furthermore, we comprehensively summarize current advances in anti-atherosclerotic drugs and bioactive compounds targeting pyroptosis, aiming to provide theoretical foundations and research perspectives for developing novel strategies for the prevention and treatment of As.