Abstract:Aim To investigate the effects of tissue factor pathway inhibitor (TFPI) on cardiomyocyte apoptosis following ischemia/reperfusion (I/R) injury. Methods I/R model was established by ligating the anterior descending coronary artery in vivo. Rats were randomly divided into three groups:the control, I/R, and I/R+rTFPI groups. HE staining was used to evaluate the morphological changes of rats myocardial tissue after reperfusion for 3 days. TTC staining was used to detect the myocardial infarct size. Ultrastructural damage in cardiomyocytes was measured by transmission electron microscopy. The expression levels of Bcl-2, Bax and cleaved Caspase-3 in rats myocardial tissue were detected by Western blot analysis. Cardiomyocytes of Sprague Dawley (SD) rats were cultured by enzyme digestion and differential adherent method in vitro experiments. Cardiomyocytes I/R injury in vitro model was established by 2 h of hypoxia and 12 h of reoxygenation using MIC101 system. Cardiomyocytes were divided into control group, H/R group, and H/R+rTFPI group (10 μg/L). Cell viability was detected by CCK-8 assay. Detection of cardiomyocytes apoptosis was performed by TUNEL technique. Western blot analysis was used to detect the expression of Bax, Bcl-2 and cleaved Caspase-3. Results A myocardial I/R model was successfully established in vivo. HE staining showed myocardiumin exhibited a higher degree of necrosis than that in control group, which was milder in I/R+rTFPI group than that in I/R group (P＜0.05). TTC staining showed that, compared with I/R group, myocardial infarct size reduced 39.76% in I/R+rTFPI group (P＜0.05). The data of transmission electron microscopy showed that the degree of apoptosis and injury was severer in I/R group than that in control group, whereas it was milder in I/R+rTFPI group than that in I/R group. Western blot detection results showed that compared with control group, the expression of Bcl-2 decreased 53.43% in I/R group(P＜0.05), but the expression of Bax and cleaved Caspase-3 increased 29.05% and 73.25% respectively (P＜0.05). After adding rTFPI, the expression of Bax and cleaved Caspase-3 in myocardial tissue decreased 13.77% and 24.25% respectively compared with I/R group(P＜0.05), whereas the expression of Bcl-2 increased 55.01% compared with I/R group (P＜0.05). In in vitro experiment, the CCK-8 results showed the cell viability of H/R group decreased 29.70% compared with control group(P＜0.05), but it increased 19.77% after adding rTFPI compared with H/R group(P＜0.05). The TUNEL detection showed that the apoptotic rate of H/R group increased 56.76% compared with control group, whereas the apoptotic rate of H/R+rTFPI group decreased 24.55% compared with H/R group(P＜0.05). Western blot results showed that compared with control group, the expression of Bcl-2 in cardiomyocytes decreased 46.92% in H/R group (P＜0.05), but the expression of Bax increased 41.90%(P＜0.05) and the expression of cleaved Caspase-3 increased 2.68 fold (P＜0.05). After adding rTFPI, the expressions of Bax and cleaved Caspase-3 in the cardiomyocytes decreased 26.34% and 57.60% respectively when compared with H/R group(P＜0.05), whereas the expression of Bcl-2 increased 28.24% compared with H/R group (P＜0.05). Conclusion TFPI served a protective role against I/R and H/R-induced cardiomyocyte injury by inhibiting apoptosis.

Abstract:Aim To investigate the effect of circ_0036167 on the fibrotic phenotype of cardiac fibroblasts and the potential mechanism involved. Methods Masson's trichrome staining was performed in the myocardium of patients with heart failure (HF) and healthy organ donors. Levels of circ_0036167 and its host gene of MYO9A were determined by real-time quantitative polymerase chain reaction (RT-qPCR) in the myocardium of HF patients and healthy organ donors. Actinomycin D treatment and RNase R exonuclease digestion were used to test the stability of circ_0036167 in AC16 cells. The myocardial fibroblasts (mCF) of C57BL/6 mice were infected with recombinant circ_0036167 adenovirus, and the expression of fibrosis related genes COL1A1, COL3A1 and ACTA2 were detected at RNA and protein levels.EdU staining and transwell migration assay were performed to detect the effects of circ_0036167 on mCF proliferation and migration activities. According to the results of bioinformatic prediction, RNA binding protein immunoprecipitation (RIP) assay was performed to confirm the interaction between circ_0036167 and fused in sarcoma (FUS) protein. Effect of FUS knockdown on inhibition of fibrosis-related genes expression by circ_0036167 in mCF was determined. ResultsMasson's trichrome staining showed that the cardiac fibrosis was significantly increased in the myocardium of HF patients (P＜0.001). Circ_0036167 was found markedly increased in the myocardium of HF patients (P＜0.05), with no significant difference in its host gene of MYO9A. In response to actinomycin D treatment and RNase R exonuclease digestion, circ_0036167 was more stable than MYO9A. Over-expression of circ_0036167 suppressed proliferation and migration of mCF, and inhibited RNA and protein expression of fibrosis-related genes in mCF. RIP assay revealed the interaction between circ_0036167 and FUS protein. Knock-down of FUS could increase fibrosis-related genes expression (P＜0.05 or P＜0.01), and significantly attenuated the inhibitory effect of circ_0036167 on fibrosis-related gene expression in mCF(P＜0.01 or P＜0.001). Conclusion FUS mediates the anti-fibrotic effect of circ_0036167 in mCF.

Abstract:Aim To study the effective components, targets and pathways of Uncaria for the treatment of atherosclerosis based on network pharmacology and molecular docking. Methods Using TCMSP database and screening conditions, the main effective components and corresponding targets of Uncaria were determined, and the effective component-target network was constructed. GeneCards, DisGeNET, OMIM and TTD databases were used to identify disease targets of atherosclerosis, and the intersection of drug targets and disease targets were obtained. PPI network analysis, GO biological function enrichment analysis and KEGG pathway enrichment analysis were performed on the intersection targets.Using “Analyze Network ”tool in Cytoscape 3.9.0, an active component-target-pathway network was constructed and the core components, core targets and core pathways were screen out. The affinity between core components and core targets were verified by molecular docking. Results Thirty-three active components were screened out, one of which had no corresponding target. A total of 1 608 disease targets and 115 drug-disease intersection targets were screened. The main targets of PPI analysis were AKT1, TNF, IL-6, IL-1β, TP53, JUN, CASP3, MMP9 and PTGS2, etc. GO biological function enrichment analysis obtained 22 items of biological processes, 57 items of cell components and 100 items of molecular function. KEGG pathway enrichment analysis screened 20 signaling pathways, mainly including lipid and atherosclerosis, MAPK, cancer signaling pathways, etc. In the effective component-target-pathway network constructed by “Analyze Network” tool, the core components of Uncaria in the treatment of atherosclerosis were selected as quercetin and kaempferol. The core targets were PTGS2, HSP90AA1 and PTGS1. The core pathways were lipid and atherosclerosis, MAPK signaling pathway. Molecular docking showed that quercetin and kaempferol had good affinity with PTGS2, HSP90AA1 and PTGS1 targets, especially PTGS2 had strong binding activity with quercetin and kaempferol. Conclusion Quercetin and kaherol, the core components of Uncaria, may act on PTGS2, HSP90AA1 and PTGS1 targets through lipid and atherosclerotic and MAPK signaling pathways, and play an anti-atherosclerotic role in the biological functions of protein binding, enzyme binding and recognized protein binding.

Abstract:Aim To explore the risk factors of major adverse cardiovascular events(MACE) after percutaneous coronary intervention (PCI) in patients with coronary artery calcification(CAC), and to construct a nomogram prediction model for MACE in CAC patientsafter PCI. Methods Retrospective analysis of clinical data of 406 patients admitted to the Department of Cardiology of the Fourth Affiliated Hospital of Xinjiang Medical University from January 2018 to December 2019, they were diagnosed with CAC by coronary angiography (CAG) or intravascular ultrasound (IVUS) and underwent PCI. The subjects were divided into event group (60 cases) and non-event group (346 cases) according to the incidence of MACE during the follow-up period. The LASSO regression and multivariate Logistic regression analysis were used to determine the independent risk factors of MACE in CAC patients after PCI, and then a nomogram prediction model was constructed and evaluated. Results LASSO regression and multivariate Logistic regression analysis results showed that advanced age, diabetes, renal dysfunction, elevated Gensini score and rotational atherectomy were risk factors for the incidence of MACE, and enlarged minimum lumen diameter (MLD) was a protective factor for the incidence of MACE (P＜0.05). The nomogram prediction model was constructed using the above six predictive indicators. After internal validation, the AUC values of nomogram for predicting MACE in CAC patients after PCI was 0.824 (95%CI:0.767～0.875), the sensitivity was 0.771, and the specificity was 0.720, suggesting that the model had a good discrimination. The calibration curve indicated that the deviation correction curve of the nomogram prediction model had good consistency with the ideal curve. The clinical decision curve analysis (DCA) suggested that when the prediction threshold of the model was in range of 0～0.6, the patient's clinical net benefit level was the highest, and the nomogram model had good clinical applicability. Conclusion The nomogram prediction model established in this study can better quantitatively assess the risk degree of MACE in CAC patients after PCI, which is helpful for clinicians to screen high-risk patients, formulate individualized targeted interventions, and improvepatients, prognosis.

Abstract:Aim To investigate the correlation of intravenous ultrasound (IVUS) with coronary artery disease and left ventricular function in patients with non-ST segment elevation acute myocardial infarction (NSTEAMI). Methods A total of 90 patients with NSTEAMI admitted to Sanshui District People's Hospital of Foshan from June 2016 to December 2021 were selected as the study subjects. They were divided into single-vessel disease group (42 cases) and multi-vessel disease group (48 cases). The independent factors influencing the exacerbation of coronary artery disease in NSTEAMI patients were analyzed, and the linear graph prediction model was constructed and evaluated. The correlation between plaque load, eccentricity index, remodeling index, fibrous cap thickness and left ventricular ejection fraction (LVEF) was analyzed. Receiver operating characteristic (ROC) curve was used to analyze the predictive value of IVUS parameters for coronary exacerbation in patients with NSTEAMI. Results Serum cystatin C (CysC) ＞1.54 mg/L (OR＝2.5,5%CI:1.377～3.047), high sensitivity C-reactive protein (hs-CRP) ＞34.25 mg/L (OR＝1.2,5%CI:1.128～2.412), plaque load ＞60% (OR＝1.9,5%CI:1.232～2.405), eccentricity index ＞6.99 (OR＝1.7,5%CI:1.035～2.164), remodeling index ＞0.99 (OR＝1.0,5%CI:1.374～3.023), fibrous cap thickness ＜0.72 mm (OR＝0.3,5%CI:0.785～0.994) and LVEF ＜58% (OR＝0.6,5%CI:0.544～0.862) were independent risk predictors of coronary exacerbation in patients with NSTEAMI (P＜0.05). Pearson's test showed that plaque load, eccentricity index and remodeling index were significantly negatively correlated with LVEF (P＜0.05), and fiber cap thickness was significantly positively correlated with LVEF (P＜0.05). The results of ROC curve showed that the area under curve (AUC) of increased plaque burden, eccentricity index, remodeling index and decreased fiber cap thickness combined to predict the aggravation of coronary artery disease was 0.887 (95%CI:0.841～0.953), which was far higher than the AUC predicted by each index alone. The results of the lipopograph model based on seven independent predictors show that the AUC was 0.839, the C-index was 0.825, Hosmer-Lemeshow goodness of fit test showed a good fit (χ²＝1.475, P＝0.386), and it had a high net benefit value. Conclusions The plaque load, eccentricity index and remodeling index of NSTEAMI patients were negatively correlated with LVEF, and the fibrous cap thickness was positively correlated with LVEF. The diagnostic value of increased plaque burden, increased eccentricity index, increased remodeling index and decreased fiber cap thickness in predicting the exacerbation of coronary artery disease is much greater than that of each index alone.

Abstract:Aim To investigate the predictive values of systemic immune-inflammation index (SII) and prognostic nutritional index (PNI) on the long-term prognosis of patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). Methods A total of 1 522 patients with ACS undergoing PCI were consecutively enrolled from January 2016 to December 2018 in the Cardiology Department of the Affiliated Hospital of Chengde Medical University. After discharge, the patients were followed up by outpatient and telephone. The endpoints were major adverse cardiovascular events (MACE) including all-cause mortality and rehospitalization for severe heart failure (NYHAⅣ) during follow-up. The cutoff values of these inflammatory markers to predict MACE were calculated using receiver operating characteristic (ROC) curves. The patients were divided into high and low SII and PNI groups via ROC curve analysis (low SII group (SII＜628.60×10⁹ L－1, n＝795) vs. high SII group (SII≥628.60×10⁹ L－1, n＝727), low PNI group (PNI≤48.15, n＝584) vs. high PNI group (PNI＞48.15, n＝938)). The 1 522 patients were divided into two groups:MACE group (n＝59) and non-MACE group (n＝1 463). The correlation between SII and PNI, and other inflammatory markers was analyzed. Kaplan-Meier curve and Cox regression models were used for survival analysis. Results The area under the ROC curve of the SII, PNI, SII+PNI, neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), monocyte to lymphocyte ratio (MLR) was 0.3,0.3,0.1,0.1,0.7,0.585 (all P＜0.05). The cumulative survival rates of the high SII and the low PNI groups were significantly lower than the low SII and the high PNI groups, respectively. SII was positively correlated with NLR (r＝0.899), PLR (r＝0.762), MLR (r＝0.446) (all P＜0.001), while PNI was negatively correlated with SII (r＝－0.450), NLR (r＝－0.545), PLR (r＝－0.589), MLR (r＝－0.458) (all P＜0.001). SII≥628.60×10⁹ L－1, PNI≤48.15 were all found to be independent indicators for predicting all-cause mortality and rehospitalization for severe heart failure (P＜0.05). Conclusion A higher SII and lower PNI value was independently associated with higher risk of developing MACE in patients with ACS undergoing PCI, which may be useful prognostic parameters to identify high-risk ACS patients after PCI.

Abstract:Aim To analyze the risk factors of hypertension with coronary heart disease after percutaneous coronary intervention (PCI) and construct a nomogram warning model for in-stent restenosis (ISR). Methods A total of 182 patients with hypertension and coronary heart disease after PCI in the Second People's Hospital of Fuyang City from June 2020 to March 2022 were selected as the research subjects, and they were divided into ISR group (n＝42) and non-ISR group(n＝140) according to whether ISR occurred after operation or not. The clinical data of the selected patients were analyzed. Univariate, LASSO and Logistic regression analysis were used to screen the risk factors for ISR after PCI with breast hypertension and coronary heart disease. According to the risk factors, a nomogram early warning model was constructed and a goodness-of-fit test was performed. Results A total of 182 patients with hypertension and coronary heart disease after PCI were included in this study, and 42 cases of ISR were confirmed by relevant tests, and the incidence rate was 23.08%. There were differences in smoking, stent diameter, stent length, high uric acid, high sensitivity C-reactive proein (hs-CRP) level, serum amyloid A (SAA) level, and lipoprotein(a) level in the two groups (P＜0.05). Logistic regression analysis showed that diabetes (OR＝4.4,5%CI:1.733～11.498, P＝0.002), long-term smoking (OR＝4.8,5%CI:1.812～11.921, P＝0.001), stent diameter ≤ 3 mm (OR＝4.4,5%CI:1.692～10.947, P＝0.002), high uric acid (OR＝2.0,5%CI:1.092～6.826, P＝0.032), hs-CRP＞10 g/L (OR＝3.3,5%CI:1.493～10.574, P＝0.006), SAA≥10 mg/L (OR＝6.8,5%CI:2.394～17.640, P＝0.000) and lipoprotein(a)≥300 mg/L (OR＝2.5,5%CI:1.209～7.319, P＝0.018) were the incidences of hypertension complicated with coronary heart disease after PCI independent risk factors for ISR. The nomogram early warning model for ISR after PCI for hypertension and coronary heart disease was established based on 7 independent risk factors. The validation results showed that the C-index was 0.864 (95%CI:0.831～0.897), the predictive value of the calibration curve was basically consistent with the measured value, the area under curve (AUC) was 0.834 (95%CI:0.806～0.862), and the decision curve showed that when the threshold probability was in the range of 3% to 100%, there was a higher net benefit value. Conclusions Diabetes mellitus, long-term smoking, stent diameter ≤ 3 mm, high uric acid, hs-CRP＞10 g/L, SAA≥10 mg/L, lipoprotein(a)＞300 mg/L are independent risks of ISR after PCI with hypertension and coronary heart disease. The nomogram model established based on the above risk factors can accurately assess and quantify the risk of ISR after PCI with hypertension and coronary heart disease.

Abstract:Extracellular vesicles are lipid bilayer-enclosed micro-vesicles generally existed in many biological fluids, and mediate molecular pathways and biological behavior of recipient cells by transferring various bioactive molecules to target cells, such as microRNA(miRNA). Recent studies have found that miRNA in extracellular vesicles plays an important role in the occurrence and development of atherosclerosis. This article reviews the selectivity of extracellular vesicular miRNA transfer in atherosclerosis, its regulatory role in the development of atherosclerosis, and its potential application in diagnosis and treatment.

Abstract:Adipose tissue browning may affect the progression of atherosclerosis. This paper first introduces the effects of ambient temperature changes on atherosclerosis, and then introduces the effects of various methods to induce adipose tissue browning on atherosclerosis, finally introduces the role of iron metabolism in adipose tissue browning and the new idea for the treatment of atherosclerosis by regulating adipose tissue browning through iron metabolism, and summarizes the research progress of the relationship between adipose tissue browning and atherosclerosis.

Abstract:Aortic dissection refers to the dissection hematoma formed when the intima of the aorta is torn by itself or external factors, and the blood in the lumen enters the middle layer of the artery wall through the intima breach. Aortic dissection is a dangerous acute disease and if the aortic dissection is completely torn, it will quickly lose blood and lead to circulatory failure and immediate death. Nonetheless, mechanistic studies of aortic dissection are currently poorly understood. Non-coding RNA is an independent RNA transcript, accounting for more than 90% of human genomic RNA. It usually does not encode protein, but acts as an important regulator to maintain normal physiological functions. So far, many studies have demonstrated that non-coding RNA are involved in the regulation of cardiovascular diseases. Therefore, much attention has been paid to the study of non-coding RNA in aortic dissection. This article reviews the mechanism of non-coding RNA in aortic dissection, and emphasizes that non-coding RNA is a biomarker of aortic dissection and a potential preventive and therapeutic means to target aortic dissection, providing a broad idea for the development of targeted drugs using non-coding RNA as a carrier in the future.

Abstract:Acute aortic dissection (AAD) is a very dangerous cardiovascular emergency. Although some progress has been made in diagnosis and treatment, the mortality rate of AAD is still high. AAD is a multi-factor involved disease, and its pathophysiological mechanism has not been fully explained, so its clinical treatment effect is limited and its mortality rate is extremely high. A large number of studies have shown that serum amyloid A (SAA), as a major inflammatory protein produced in the acute phase response, is closely related to the occurrence and development of cardiovascular diseases.Therefore, SAA may become a candidate target for the diagnosis and treatment of AAD. This review discusses the relationship between SAA and inflammatory response, vascular dysfunction, thrombosis and extracellular matrix remodeling, and the possibility of SAA as a potential biomarker of AAD.