Abstract:Protein palmitoylation is a kind of post-translational lipid modification of proteins that widely exists in organisms. Generally, S-palmitoylation occurs mainly through the covalent attachment of palmitic acid to protein-specific cysteine residues via labile thioester linkages. S-palmitoylation is usually reversible because the thioester bond will be hydrolyzed under certain conditions, causing protein depalmitoylation. In addition, S-palmitoylation is closely associated with the occurrence and development of many cardiovascular diseases. This review summarizes the process of protein palmitoylation and depalmitoylation, the relationship between protein palmitoylation and cardiovascular diseases, including arrhythmia, atherosclerosis, pulmonary hypertension, heart failure, and thrombotic diseases, which provide a new direction for cardiovascular disease treatment.

Abstract:Aim To predict the anti-atherosclerotic targets and signal pathways of Morinda officinalis by using traditional Chinese medicine system pharmacology, small molecule drug target prediction and disease genome database, and combined with the molecular docking technology. Methods The technology platform of Chinese medicine system pharmacology (TCMSP) and the online platform for small molecule drug target prediction (Swiss Target Prediction) were used to explore the active components of Morinda officinalis and the targets of its response. GeneCards, OMIM, Disgenet and UniProt were used to collect and screen the disease targets related to atherosclerosis. The intersection genes were obtained and imported into the String 11.5 database to construct the disease-drug protein-protein interaction (String-PPI) network map. Cytoscape 3.9.1 software was used to visualize key target networks. Then, GO and KEGG enrichment were performed using Metascape online platform to explore the molecular targets of anti-atherosclerosis, the pathway map was drawn through KEGG database. Finally, Autodock vina 1.1.2 software was used to verify the molecular docking of core compounds and target genes of Morinda officinalis. Results A total of 17 effective drug compounds including β-sitosterol and anthraquinone, 73 core targets and 1 450 key disease genes were collected from the above databases, then 35 core genes of Morinda officinalis acted on atherosclerosis were obtained after the intersection. 32 genes including SRC, PGTS2, TGFβ1, REN, ESR1 and CASP3, were identified by String-PPI. KEGG enriched 75 signaling pathways, involving lipid-atherosclerosis, advanced glycosylation end products and receptors and PI3K-Akt signaling pathway, among which lipid-atherosclerosis pathway mainly involves six target genes such as SRC, BCL2, BAX, CASP3, GSK3B and RXRA. Molecular docking showed that the main chemical components of Morinda officinalis had strong binding activity with core genes. Conclusion Morinda officinalis can regulate the expression of 32 major genes including SRC, PGTS2, TGFβ1, REN, RXRA,ESR1, CASP3 through β-sitosterol, anthraquinone and other major chemical components, controls vascular endothelial inflammation and inhibits cell proliferation, migration and apoptosis, therefore plays the certain role of anti-atherosclerosis.

Abstract:Aim To observe the effect of cardiac glucocorticoid receptor activation on cardiac remodeling and cardiac function after myocardial infarction (MI) in mice and its possible mechanism. Methods 28 male C57BL/6J mice were randomly divided into sham group, dexamethasone group, MI group and MI＋dexamethasone group, 7 mice in each group. The MI group ligated the left anterior descending coronary artery in mice to create an MI model; the sham group and the dexamethasone group only wound the thread without ligation, and injected normal saline or dexamethasone (20 mg/kg) by intraperitoneal injection 24 h before the operation; the MI＋dexamethasone group was injected with dexamethasone (20 mg/kg) by intraperitoneal injection 24 h before creating MI model. On the 7th day after surgery, small animal ultrasound was used to detect cardiac function indicators, heart tissue slices were taken and immunohistochemical staining was used to observe the activation level of glucocorticoid receptors, Masson staining was used to observe the infarct area, immunohistochemical staining was used to observe the levels of inflammatory factor IL-6 and chemokine CCL-5. Results Compared with the MI group, in the MI+dexamethasone group the left ventricular end-diastolic diameter reduced by 6.85%, the left ventricular end-systolic diameter reduced by 6.89%, the left ventricular end-diastolic volume reduced by 16.11%, the left ventricular end-systolic volume reduced by 17.18% (all P＜0.05), the ejection fraction increased by 10.63%, and the fractional shortening rate increased by 13.11% (all P＜0.05), indicating that dexamethasone pretreatment improved cardiac function in mice after MI; the level of phosphorylated glucocorticoid receptor increased 1.57 times; after MI, the infarct area decreased by 18.4% (P＜0.05); the expression level of inflammatory factor IL-6 decreased by 71.4%, and the expression level of chemokine CCL-5 decreased by 65% (all P＜0.05). Conclusion Activation of cardiac glucocorticoid receptors has an antagonistic effect on myocardial cell damage in mice after MI, which can improve myocardial remodeling, this effect may be related to its anti-inflammatory response.

Abstract:Aim To investigate the effect of lncRNA NEAT1 on myocardial fibrosis in rats with atrial fibrillation (AF) by regulating miR-27b-3p/specific protein 1 (SP1) axis. Methods 54 rats were divided into six groups (n＝9) according to the random number table method:sham group, AF group, AF＋shControl group, AF＋shNEAT1 group, AF＋shNEAT1＋anti-miR-Control group and AF＋shNEAT1＋anti-miR-27b-3p group. After 2 weeks of transfection with the above lentiviral vector, AF rats was established by tail vein injection of acetylcholine-CaCl₂ for 7 days. The incidence and duration of AF were recorded by electrocardiogram; the expression levels of NEAT1, miR-27b-3p, SP1 and fibrosis-related genes (TGF-β1, CTGF, COLⅠ, COLⅢ) in atrial tissue were detected by RT-qPCR; the luciferase report gene confirmed the targeting relationship between miR-27b-3p and NEAT1, and miR-27b-3p and SP1; cardiomyocyte apoptosis in atrial tissue was observed by TUNEL staining; myocardial fibrosis in atrial tissue was observed by Masson staining; and the protein expression levels of SP1 and fibrosis-related genes in atrial tissue were detected by Western blot. Results Compared with the AF group, the incidence and duration of AF, myocardial fibrosis, apoptosis and the mRNA and protein expression of TGF-β1, CTGF, COLⅠ and COLⅢ were significantly decreased in AF＋shNEAT1 group (P＜0.05). NEAT1 negatively regulates the expression of miR-27b-3p. Silencing miR-27b-3p reversed the inhibitory effects of shNEAT1 on myocardial apoptosis and fibrosis in AF rats. miR-27b-3p directly targeted SP1 and inhibited its mRNA and protein expression. NEAT1 promoted SP1 expression by down-regulating miR-27b-3p. Conclusion Down-regulation of NEAT1 can alleviate AF and AF-induced myocardial fibrosis, and its regulatory mechanism is related to the regulation of miR-27b-3p/SP1 axis.

Abstract:Aim To investigate the potential mechanisms and immunological correlation of below-the-knee atherosclerosis obliteran (BTK). Methods The GSE100927 dataset was downloaded from the Gene Expression Omnibus.Differentially expressed genes of BTK were screened by using “limma” package of the R and weighted correlation network analysis (WGCNA). Signaling pathway enrichment analysis was performed by “clusterProfiler” package of the R. The protein-protein interaction network was constructed, and the core genes associated with BTK were screened. The differences of the core genes’ expression between the BTK samples and normal samples were analyzed, and the area under the receiver operating characteristic curve was used to evaluate the diagnostic efficacy of the core genes. The CIBERSORT was used to evaluate the distribution of immune cells in each sample and to calculate the differences between the BTK samples and normal samples. Results 153 genes were up-regulated and 63 genes were down-regulated in BTK. WGCNA results indicated that the differential expression genes in BTK were mainly up-regulated, involving signaling pathways such as cholesterol metabolism and platelet activation; protein tyrosine phosphatase receptor type C (PTPRC), Spi-1 proto-oncogene (SPI1),colony stimulating factor 1 receptor (CSF1R), and Fc gamma receptor Ⅲa (FCGR3A) were probably the core genes in BTK, which have good diagnostic efficacy. BTK was positively correlated with the degree of infiltration of monocytes (r＝0.419, P＝0.037) and negatively correlated with the degree of infiltration of M2 macrophages (r＝－0.491, P＝0.013). Conclusion The BTK involved various signaling pathways such as cholesterol metabolism and platelet activation and was closely related to monocyte- and macrophage-mediated immune responses. PTPRC, SPI1, CSF1R, and FCGR3A may be the core genes of BTK.

Abstract:Aim To investigate the relationship between the triglyceride-glucose (TyG) index and major adverse cardiovascular and cerebrovascular events (MACCE) in the acute coronary syndrome(ACS) patients underwent emergency percutaneous coronary intervention (PCI) with drug-eluting stents. Methods Overall, 2 249 patients with ACS underwent emergency PCI were enrolled in this study. The patients were divided into high TyG index group and low TyG index group according to the median TyG index. The incidence of endpoint events as follows:all-cause death, non-fatal myocardial infarction(MI), non-fatal ischemia stroke, and ischemia-driven revascularization were determined and compared between two groups.Unitivariate and multivariate Cox analysis were used to evaluate the predictive value of the TyG index for MACCE. Subgroup analysis was used to evaluate the consistency of the predictive value of the TyG index for MACCE. Results Overall, 299 (13.3%) endpoint events were documented during a 66-month follow-up. Compared with the low TyG index group, the high TyG index group had a significantly higher incidence of MACCE (17.1% vs. 9.5%, P＜0.001), all-cause death (6.2% vs. 3.7%, P＝0.007), cardiac death (4.4% vs. 2.1%, P＝0.002), non-fatal MI (1.0% vs. 0.3%, P＝0.001), non-fatal ischemia stroke (2.0% vs. 1.0%, P＝0.039) and ischemia-driven revascularization (7.8% vs. 4.8%, P＝0.001). The multivariable Cox regression analysis further revealed that the TyG index was an independent predictor of MACCE (hazard ratio (HR)1.0,5% confidence interval (CI) 1.304～2.242,P＜0.001). The results of subgroup analysis showed that the predictive effect of TyG index on MACCE still existed in different subgroups. Conclusion The TyG index might be an independent predictor of MACCE in patients with ACS underwent emergency PCI with drug-eluting stents.

Abstract:Aim To investigate the serum plasminogen activator inhibitor-1 (PAI-1) level in patients with obstructive sleep apnea hypopnea syndrome (OSAHS) and its correlation with carotid intima-media thickness(CIMT) and plaque stability. Methods 167 patients who underwent polysomnography (PSG) in Baoji Municipal Central Hospital from July 2019 to January 2021 were enrolled and divided into control group (n＝46), mild OSAHS group (n＝15), moderate OSAHS group (n＝39), and severe OSAHS group (n＝67) according to sleep apnea-hypopnea index (AHI). Clinical data, PSG-related indexes, blood biochemical indicators, serum PAI-1 level, and CIMT were compared in the three groups. The relationship between CIMT and serum PAI-1 concentration in OSAHS patients was analyzed. According to CIMT, carotid plaque morphology, and ultrasonographic features, OSAHS patients were divided into simple OSAHS group (n＝37), OSAHS stable plaque group (n＝46), and OSAHS unstable plaque group (n＝38). PAI-1 level in each group was compared. Multivariate Logistic regression analysis was used to explore the risk factors of carotid plaque stability in OSAHS patients. Results There were statistically significant differences between the four groups regarding sex, body mass index (BMI), hypertension, smoking history, AHI, oxygen depletion index (ODI), oxygen saturation less than 90% of the time in sleeping time (Ts90%), the lowest nocturnal oxygen saturation (L-SaO₂), CIMT and serum PAI-1 level (P＜0.05). Pearson correlation analysis showed that CIMT was positively correlated with PAI-1 level in OSAHS patients (r＝0.675,P＜0.001). The level of PAI-1 in the simple OSAHS group was 1.20 times, in the OSAHS stable plaque group was 1.79 times, and in the OSAHS unstable plaque group was 2.01 times that of the control group, and the difference had statistical significance (all P＜0.05). Multiple linear regression suggested that CIMT was independently associated with AHI (B＝0.019, P＝0.001), PAI-1 (B＝0.012, P＜0.001), and low density lipoprotein cholesterol (LDLC)(B＝0.081, P＝0.028) after calibrating confounders. Multivariate Logistic regression analysis showed that after calibrating confounders, hypertension (OR=4.1,5%CI:2.034～18.117), diabetes (OR=1.0,5%CI:1.158～3.645), PAI-1 level (OR=1.1,5%CI:1.039～1.145), moderate OSAHS (OR=1.7,5%CI:1.162～3.730), severe OSAHS (OR=5.4,5%CI:1.085～31.370) were independent risk factors for unstable carotid plaque in patients with OSAHS (P＜0.05). Conclusion The level of PAI-1 might increase gradually accompanied by the severity of OSAHS and the level of PAI-1 might be positively correlated with CIMT. PAI-1 might be an independent risk factor for unstable arterial plaque in OSAHS.

Abstract:Aim To investigate the correlation between urinary albumin (UAlb) level and coronary artery calcification (CAC) in patients with chronic kidney disease (CKD) undergoing peritoneal dialysis (PD). Methods 186 CKD patients hospitalized in Xianyang Central Hospital for PD treatment from February 2020 to June 2022 were selected as research objects and included in the training set; according to Rumberger CAC grading method, they were divided into non-calcification group (0～10 points, 80 cases) and calcification group (＞10 points, 106 cases); according to the same criteria, 62 CKD patients hospitalized in Xianyang Central Hospital for PD treatment from July 2022 to November 2022 were included in the validation set. The clinical data of the two groups were compared and analyzed. The threshold effect of UAlb was determined by curve fitting and threshold effect analysis. Multivariate Logistic regression was used to analyze the risk factors affecting the occurrence of CAC, and an nomogram prediction model was constructed and evaluated. Results When UAlb＞30 mg/L, the risk of CAC increased with the increase of its level. Age＞50 years old, dialysis time＞20 months, diabetes, neutrophil-to-lymphocyte ratio (NLR)≥3.5, phosphorus≥1.8 mmol/L, and UAlb＞30 mg/L were independent risk factors for CAC (P＜0.05). The evaluation results showed that the discrimination, accuracy and effectiveness of the nomograph prediction model were high. Conclusions When UAlb＞30 mg/L, the risk of CAC increases with its level. Age＞50 years old, dialysis time＞20 months, diabetes, NLR≥3.5, phosphorus≥1.8 mmol/L, UAlb＞30 mg/L are all independent risk factors for CAC.

Abstract:With the development of population aging and urbanization, the morbidity and mortality of cardiovascular diseases are continuously increasing, posing a serious threat to human life, health and safety. The onset and course of cardiovascular diseases are affected by many factors, and the dysregulation of intestinal flora as one of them has attracted a lot of attention. Intestinal flora is a microflora that exists in the gastrointestinal tract and has a mutually-beneficial symbiosis with the human body. More and more studies have shown that the intestinal flora and cardiovascular diseases interact with each other, and the two are mutually causal, targeted intervention of cardiovascular diseases by regulating intestinal flora can become a new therapeutic idea. Modern studies have found that traditional Chinese medicine (TCM) compounds, TCM monomers and acupuncture can effectively correct the dysregulation of intestinal flora, up-regulate the number of probiotics, restore intestinal barrier function and reduce inflammation. Based on the above studies, this paper summarized the interaction between intestinal flora and its metabolites and cardiovascular diseases, and also summarized the therapeutic effects of some TCM in regulating intestinal flora, restoring the dynamic balance of intestinal flora, treating the heart with intestines and intervening in cardiovascular diseases, in order to provide new ideas and feasible schemes for the prevention and treatment of cardiovascular diseases.

Abstract:Venous thromboembolism (VTE), including pulmonary embolism (PE) and deep vein thrombosis (DVT), is considered as one of the most common cardiovascular diseases in the world, causing a huge social and economic burden. Despite the predominant role in the treatment of VTE, anti-thrombotic therapy has an extremely high risk of bleeding due to its association with blood coagulation and hemolysis system. Therefore, strict monitoring should be performed during the disease progression. However, the existing approaches can not fully meet the needs of precision medicine. Molecular imaging can reflect the disease information at the molecular level. Quantitative monitoring on thrombus-targeted nanoprobes through imaging approaches can accurately diagnose disease subtypes and provide personalized treatment. This article reviews the research progress of nanomolecular imaging in the diagnosis and treatment of VTE in recent years, which is expected to provide new ideas for the diagnosis and treatment of VTE.

Abstract:Homocysteine (Hcy) is an intermediate metabolite of methionine metabolism, and a large number of studies have found that Hcy is closely related to cardiovascular diseases. MicroRNA(miRNA) is a large class of short-chain non-coding RNA, it has been confirmed in a variety of diseases that miRNA disorder can lead to disease progression, such as immune disorders, diabetes, epilepsy, cancer, etc. At present, miRNA is considered as a new treatment strategy for cardiovascular diseases due to its crucial role in the cardiovascular system. The current study has confirmed that both Hcy and miRNA are risk factors for cardiovascular disease, but the role of Hcy and miRNA interaction in cardiovascular disease remains to be elucidated. This paper briefly reviews the progress and potential clinical application of Hcy regulated miRNA in cardiovascular diseases.

Abstract:Irisin is mainly a muscle cytokine produced and secreted by muscle cells after exercise, and is also expressed in the adipose tissue, liver, pancreas, testes, stomach, and other tissues. Irisin is derived from the fibronectin type Ⅲ domain containing 5 (FNDC5) through its extracellular fragment proteolytic cleavage and secreted in the peripheral circulation. Irisin converts white adipose tissue into brown adipose tissue, increases mitochondrial metabolism and energy expenditure, ameliorates insulin resistanc, differentiates neural and proliferates osteoblasts through signaling pathways such as MAPK, AMPK, PI3K/Akt and STAT3/Snail. And it is expected to become a new target for the treatment of glycolipid metabolism related diseases.