Abstract:Exosomes are the means of intercellular communication, and long non-coding RNAs (lncRNA), as the cargo of exosomes, are involved in regulating various physiological and pathological processes of cardiovascular system due to their rich functions. This article reviews the relevant research on extracellular lncRNA in the field of acute myocardial infarction, summarizes the regulatory role of extracellular lncRNA, analyzes the current research status of extracellular lncRNA as a biomarker and treatment strategy for myocardial infarction, and selects potential biomarkers through sequencing information in public databases.

Abstract:Aim To explore the preventive effect and potential mechanism of β-blockers in vascular aging of spontaneously hypertensive rat (SHR). Methods 24 three-month-old male spontaneously hypertensive rats were randomly divided into placebo group, nifedipine group, nifedipine＋metoprolol group and metoprolol group, treated with edible starch, 60 mg nifedipine sustained-release tablets, 40 mg nifedipine sustained-release tablets＋75 mg metoprolol sustained-release tablets and 150 mg metoprolol sustained-release tablets, respectively. The rats fed with common diets for 9 months, and the blood pressure, heart rate and other general condition of the rats were dynamically measured. HE staining was used to observe the morphological characteristics of femoral aorta in rats. The vasomotor function of isolated femoral artery was tested by circumferential perfusion, immunofluorescence histological staining and real-time polymerase chain reaction (RT-PCR) were used to determine the expression of aging related genes p53 and p21, as well as endoplasmic reticulum stress related genes CHOP and XBP1. Results Compared with placebo group, systolic blood pressure decreased by about 30%, diastolic blood pressure decreased by about 20%, and heart rate decreased by 9%, 36% and 41% (all P＜0.01) in nifedipine group, nifedipine＋metoprolol group and metoprolol group, respectively. Compared with placebo group, the systolic and diastolic functions of nifedipine group, nifedipine＋metoprolol group and metoprolol group were significantly improved and the intima-media thickness decreased by 24%, 14% and 37% (all P＜0.01), respectively. Compared with nifedipine group and nifedipine＋metoprolol group, the systolic and diastolic functions of metoprolol group were significantly improved and the intima-media thickness decreased by 18% and 27% (all P＜0.01), respectively. Compared with the placebo group, the expression levels of p53 protein, p53 mRNA, p21 protein, p21 mRNA, CHOP protein, CHOP mRNA, XBP1 protein and XBP1 mRNA in nifedipine group decreased by 35% (P＜0.01), 23% (P＜0.05), 25% (P＜0.01), 3% (P＞0.05), 51% (P＜0.01), 24% (P＞0.05), 21% (P＜0.01) and 23% (P＞0.05), the nifedipine＋metoprolol group decreased by 36% (P＜0.01), 42% (P＜0.01), 4% (P＞0.05), 24% (P＜0.05), 32% (P＜0.01), 44% (P＜0.05), 13% (P＜0.01) and 42% (P＜0.05), the metoprolol group decreased by 47% (P＜0.01), 43% (P＜0.01), 42% (P＜0.01), 49% (P＜0.01), 78% (P＜0.01), 56% (P＜0.01), 32% (P＜0.01) and 81% (P＜0.01). Compared with nifedipine group and nifedipine＋metoprolol group, metoprolol group further inhibited the expression of genes related to aging and endoplasmic reticulum stress. Conclusions The arteries of spontaneously hypertensive rats show significant aging. β-blockers are better than calcium channel blockers in inhibiting vascular aging of spontaneously hypertensive rats, and at high doses β-blockers improve the degree of vascular aging better than combination therapy, and their mechanism may be related to the inhibition of endoplasmic reticulum stress.

Abstract:Aim To investigate the effect of butorphanol on neuronal pyroptosis in ischemic stroke rats and its role in protein kinase A (PKA)/cyclic adenosine phosphate (cAMP) response element binding protein (CREB). Methods A rat model of ischemic stroke was established using SD rats. All rats were divided into control group, model group, butorphanol low-dose group (butorphanol L group), butorphanol high-dose group (butorphanol H group) and butorphanol+PKA inhibitor (H-89) group. Neurological function was scored, TTC staining was used to detect cerebral infarction volume, and pathological characteristics of brain tissue were detected by HE staining. Neuronal pyroptosis was observed by uranium lead double staining in hippocampus. The expression of inflammassome NOD-like receptor thermal protein domain associated protein 3(NLRP3) and Caspase-1 were detected by immunofluorescence, and the contents of interleukin-1β (IL-1β), IL-18 and cAMP were detected by enzyme linked immunosorbent assay (ELISA). The expression levels of phosphorylated PKA (p-PKA), PKA, p-CREB and CREB protein were detected by Western blot. Results Compared with the control group, the brain space of rats in the model group was enlarged, the neuron cell membrane was defective, the nucleus and nuclear membrane were sunken and constricted, and the nerve function scores, cerebral infarction volume, NLRP3, Caspase-1, IL-1β and IL-18 levels were increased; the expression levels of cAMP, p-PKA/PKA and p-CREB/CREB protein were decreased (P＜0.05). Compared with the model group, the brain structure of butorphanol L and H groups was more complete, the neuronal cell structure was improved, the neural function scores, cerebral infarction volume, NLRP3, Caspase-1, IL-1β and IL-18 levels were decreased, and the protein expression levels of cAMP, p-PKA/PKA and p-CREB/CREB were increased (P＜0.05). Compared with butorphanol H group, butorphanol+H-89 group increased vacuolar degeneration of brain tissue, abnormal neuronal structure, neural function scores, cerebral infarction volume, NLRP3, Caspase-1, IL-1β and IL-18 levels; and the expression levels of cAMP, p-PKA/PKA and p-CREB/CREB protein were decreased (P＜0.05). Conclusion Butorphanol significantly inhibits neuronal pyroptosis in ischemic stroke rats, which may be related to the activation of PKA/CREB signaling pathway.

Abstract:Aim To summarize the gene mutation analysis and clinical treatment of a Chinese familial hypercholesterolemia family. Methods The proband was admitted to hospital due to “repeated asthma with chest pain for 4 months, aggravated for 2 days”, abnormally elevated plasma low density lipoprotein cholesterol (LDLC) and early onset of coronary heart disease. Whole exon sequencing was performed in the proband, and apolipoprotein E (ApoE), paraoxonase1(PON1), proprotein convertase subtilisin/kexin type 9 (PCSK9) and other sites were sequentially analyzed, and suspected pathogenic mutations were detected in family members. Coronary intervention and lipid-lowering therapy were performed in the proband and his father. Results The proband, his father and his son all had six mutations in the LDLR gene including c.191+13G＞A(rs200621482), c.1598G＞T(rs200427089), c.883T＞G(rs553235458), c.3536A＞G(rs201300867), c.2215+6G＞A(rs540060615), c.162+5A＞T(rs146596406), respectively. Heterozygous mutations were found in all 6 loci of the three patients. The ApoE genotypes of the three patients were as follows:ApoE genotypes of both the proband and his son were ε3/ε3, and the protein phenotype was E3 (CC at ApoE2 and TT at ApoE4); ApoE genotypes of his father was ε2/ε3, and the protein phenotype was E2(CT at ApoE2 and TT at ApoE4). The PON1(A575G, rs662) locus genotypes of three patients were AG, and the PCSK9 genotypes of three patients were GG, CC, CC and GG.Based on the results of the family genetic test, the proband and his father were given an individualized lipid-lowering regimen, atorvastatin calcium combined with ezetimibe and PCSK9 inhibitors, and the proband and his father were successfully treated with coronary interventionary therapy, and LDLC was normal with no adverse drug reactions during follow-up of two years. Conclusion In this study, 6 mutations of LDLR gene were found in all patients of this family, among which LDLR c.191+13G＞A and c.162+5A＞T were not reported in China, which enriched the mutation spectrum of LDLR gene in Chinese population. This study is helpful to elucidate the pathogenesis of FH and further guide the clinical treatment of FH patients.

Abstract:Aim To investigate the correlation between blood lipid level and the severity of coronary artery calcification (CAC) in peritoneal dialysis (PD) patients with chronic kidney disease (CKD). Methods 205 CKD patients treated with PD in our hospital from June 2018 to December 2021 were selected as the study subjects, according to the CAC scores, they were divided into calcified group (n＝152) and non-calcified group (n＝53), and the patients in calcified group were divided into mild calcification group (n＝61), moderate calcification group (n＝50), and severe calcification group (n＝41). The differences in clinical data and laboratory indicators were compared through univariate analysis. The restricted cubic spline fitting Logistic regression model was used to analyze the relationship between blood lipid levels and CAC. Multiple Logistic regression model was used to analyze the influencing factors, receiver operating characteristic (ROC) curve was drawn to explore the predictive value of blood lipid levels for the severity of CAC. Results Compared with the non-calcified group, the age, diabetes ratio, body mass index(BMI), triglyceride(TG), total cholesterol(TC), low density lipoprotein cholesterol(LDLC), and blood phosphorus levels increased significantly in the calcified group, the levels of uric acid(UA), high density lipoprotein cholesterol(HDLC), blood magnesium, and 25-hydroxyvitamin D₃ (25-(OH)-VitD₃) were significantly reduced (P＜0.05); Logistic regression showed that adjusted TC(OR=1.9,5%CI:1.56~2.10), TG(OR=2.3,5%CI:1.86~2.41), HDLC(OR=0.7,5%CI:0.42~0.84), LDLC(OR=2.1,5%CI:1.78~2.32) were still a risk factor for the occurrence of CAC after adjusting for age, diabetes and other factors, and as the levels of TG, TC, and LDLC increased, the levels of HDLC decreased, and their correlation effect values also increased correspondingly (P_trend＜0.05). Compared with the mild calcification group, the age, TG, and TC of the moderate and severe calcification groups significantly increased, HDLC significantly decreased, UA significantly increased in the moderate calcification group, LDLC and blood phosphorus significantly increased in the severe calcification group, while blood magnesium and 25-(OH)-VitD₃ significantly decreased; Compared with the moderate calcification group, the severe calcification group showed a significant increase in TC and LDLC, while UA and HDLC decreased significantly (all P＜0.05). And the multiple Logistic regression model showed that older age, higher levels of TG, TC, LDLC, and lower level of HDLC were independent risk factors for severe CAC in CKD patients after PD treatment (P＜0.05). Restrictive cubic spline regression analysis showed a significant correlation between blood lipid levels and the severity of CAC. ROC curve analysis showed that the AUC of TG, TC, HDLC, and LDLC combined detection was 0.897, with a sensitivity of 0.899, and a specificity of 0.826. This indicated that the predictive value of TG, TC, HDLC, and LDLC combined detection for the severity of CAC in CKD patients undergoing PD treatment was higher than any single indicator. Conclusion The increased levels of TG, TC, LDLC and decreased level of HDLC were significantly associated with the risk of CAC in CKD patients undergoing PD treatment, they were also involved in the occurrence and development of CAC, and their predictive value can be improved through joint examinations in clinical practice.

Abstract:Aim To investigate the factors influencing carotid artery calcification in patients with ischemic stroke and to construct a predictive model for columnar plots to provide reference for clinical formulation of prevention and control measures. Methods A total of 500 patients with ischemic stroke were randomly divided into modeling group (350 cases) and verification group (150 cases) according to a ratio of 7∶3, and the incidence of carotid artery calcification was analyzed. LASSO-Logistic regression equation was used to analyze the influencing factors of carotid artery calcification, and the prediction model of carotid artery calcification risk was built. Receiver operating characteristic (ROC) curve and calibration curve were used to analyze the nomogram to predict model differentiation and accuracy. Decision curve analysis (DCA) was drawn to evaluate the validity of the prediction model. Results In the modeling group, compared with those without carotid artery calcification, the age of those with carotid artery calcification increased by 17.87%, the proportion of smoking history increased by 32.69%, the level of fasting blood glucose increased by 22.47%, the level of glycated hemoglobin increased by 0.69%, and the level of low density lipoprotein cholesterol (LDLC) increased by 17.84%, the uric acid level increased by 22.42%, the high sensitivity C-reactive protein (hs-CRP) level increased by 40.31%, and the estimated glomerular filtration rate (eGFR) level decreased by 7.04%, with statistical significance (P＜0.05). In the verification group, compared with those without carotid artery calcification, the age of those with carotid artery calcification increased by 17.23%, the proportion of smoking history increased by 33.39%, the level of fasting blood glucose increased by 22.37%, the level of glycated hemoglobin increased by 0.75%, the level of LDLC increased by 17.96%, and the level of uric acid increased by 24.44%, hs-CRP level increased by 30.81%, eGFR level decreased by 6.46%, the difference was statistically significant (P＜0.05). In the modeling group and the verification group, the prediction models of carotid artery calcification were constructed based on the above factors, and the AUC for predicting carotid artery calcification was 0.953 and 0.972, respectively, which was accurate and clinically effective. Conclusion Increasing age, smoking history and increased fasting blood glucose, glycated hemoglobin, LDLC, uric acid and hs-CRP levels are independent risk factors for the occurrence of carotid artery calcification, and elevated eGFR levels are independent protective factor. The prediction model based on the above factors has certain predictive value for the occurrence of carotid artery calcification.

Abstract:Aim To identify the risk factors for no-reflow (NR) associated with post-stenting balloon dilatation (PSBD) among patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI) and their impact on prognosis. Methods This study enrolled 147patients with STEMI who received emergency PCI and underwent PSBD within 12 hours. The patients were divided into the normal flow group and NR group based on their TIMI thrombus scores. Clinical data, angiography characteristics, efficacy after interventional therapy, and major adverse cardiovascular events (MACE) within one year after therapy were analyzed and compared between the two groups. Age, identified time to PCI, length of the offender's blood vessels, number of stent implants, and high-burden thrombus formation were analyzed to explore risk factors for NR after PSBD by regression analysis. The relationship between NR and the occurrence of MACE at one year after operation was analyzed to explore the influence of risk factors on prognosis. Results Sixteen patients (10.88%) had NR after PSBD. Univariate analysis revealed the correlation of age, identified time to PCI, length of the offender's blood vessels, number of stents, and high-burden thrombus formation with the incidence of NR associated with balloon dilatation (P＜0.05). Multiple Logistic analysis revealed that identified time to PCI (OR:0.5,5%CI:0.92～0.99), length of the offender's blood vessels (OR:0.6,5%CI:0.93～0.99) and high-burden thrombus formation (OR:0.4,5%CI:0.03～0.71) were independent risk factors of NR associated with PSBD. Conclusions Prolonged time to PCI, increased length of the offender's blood vessels, and heavy high-burden thrombus formation are positively correlated with the occurrence of NR after PSBD, and are independent risk factor of NR associated with PSBD for STEMI. The incidence of NR after PSBD was positively correlated with the incidence of recurrent angina in 1-year follow up.

Abstract:Aim To explore the predictive value of serum D-dimer and the soluble receptor for advanced glycation end products (sRAGE) levels in the short-term poor prognosis of elderly patients with coronary heart disease after percutaneous coronary intervention (PCI). Methods The clinical data of 316 elderly patients with coronary heart disease first diagnosed in Huanggang Central Hospital from April 2019 to June 2020 were collected. According to whether the patients had major adverse cardiovascular events (MACE) during the follow-up period, they were divided into MACE group (n＝52) and non MACE group (n＝264). The independent influencing factors of postoperative MACE were analyzed by univariate analysis and multivariate Logistic regression, the nomogram prediction model was established and verified according to the independent influencing factors of patient prognosis. The threshold effect of D-dimer and sRAGE levels was determined by curve fitting and threshold effect analysis, and the influence of D-dimer and sRAGE levels on MACE was evaluated by Kaplan-Meier curve. Results During the one-year postoperative period, 52(16.46%) of the 316 elderly patients with coronary heart disease who were included experienced MACE. Body mass index (BMI), proportion of hypertension, proportion of diabetes, GRACE score, number of stents, apoliporotein (Apo) B, ApoB/ApoA, low density lipoprotein cholesterol (LDLC), liporotein (a) [Lp(a)] and D-dimer levels of patients in the MACE group were higher than those in the non MACE group, and sRAGE levels were lower than those in the non MACE group, with statistically significant differences(P＜0.05). Multivariate Logistic regression analysis showed that high GRACE score, high Lp(a) and high D-dimer levels were independent risk factors for MACE in elderly patients with coronary heart disease after PCI treatment, and high sRAGE level was protective factor (P＜0.05). Curve fitting found that the probability of MACE increased with the increase of D-dimer level and the decrease of sRAGE level. The Kaplan-Meier curve shows that the incidence of MACE in patients with higher D-dimer levels is significantly higher than that in patients with low D-dimer levels (P＜0.001), and the incidence of MACE in patients with lower sRAGE levels is significantly higher than patients with higher sRAGE levels (P＜0.001). The nomogram model was constructed based on independent prognostic factors, and its consistency index was 0.796 (95%CI:0.723～0.834), ROC curve AUC was 0.851 (95%CI:0.806～0.892), which has a good degree of discrimination. Conclusion High level of D-dimer and low level of sRAGE are important risk factors for MACE after PCI in elderly patients with coronary heart disease, and have a high predictive value for short-term adverse prognosis after PCI.

Abstract:Endothelial dysfunction, a common feature of various cardiovascular diseases, is closely associated with the overexpression of reactive oxygen species (ROS)/reactive nitrogen species (RNS). The reaction between superoxide anion and nitric oxide (NO) can generate peroxynitrite with stronger oxidation ability, which can deplete NO by oxidizing various proteins, leading to endothelial contraction and relaxation dysfunction, and playing an important role in various cardiovascular diseases. This article reviews the pathways through which nitrosylation modified proteins are produced and the possible mechanisms by which they promote endothelial dysfunction in cardiovascular disease. It discusses the relationship between ROS/RNS mediated nitrosylation modification and endothelial dysfunction, which together promote the progression of cardiovascular disease. The article also discusses the application of therapeutic strategies such as clearing peroxynitrite, inhibiting ROS production pathways, and directly enhancing endothelial cell function in cardiovascular diseases related to endothelial dysfunction, which can provide reference for further research on the role of protein nitration modification as a post-translational intervention target in cardiovascular diseases.

Abstract:Hypoxia inducible factors (HIF) are hypoxia-sensitive transcription factors that are the primary regulators of the cellular response to hypoxia. Hypoxia inducible factors induce inflammation, lipid metabolism, endothelial dysfunction, proliferation of vascular smooth muscle cells (VSMC), and regulate the development of cardiovascular diseases (CVD). This paper reviews the role of hypoxia inducible factors in CVD and the progress of the mechanism of action in recent years, and discusses the role and mechanism of hypoxia inducible factors on vascular constituent cell types and its relationship with the occurrence and development of CVD. It can provide a reference for analyzing the pathogenesis of CVD and discovering new therapeutic targets. The aim is to provide a theoretical reference for further understanding the role and mechanism of hypoxia inducible factors in the pathogenesis of CVD, and to provide a basis for the design of novel effective therapeutic agents targeting hypoxia inducible factors.

Abstract:Atherosclerosis (As) is a pathological process caused by a complex set of factors, including endothelial dysfunction, lipid deposition in the arterial vessel wall, macrophage infiltration, smooth muscle cell dysfunction, and foam cell formation, in which inflammatory response plays an indispensable role. NOD-like receptor protein 3(NLRP3) inflammasomes are transducers of inflammatory cells, and NLRP3 inflammasome activation mediates the inflammatory response and activates downstream interleukin-18 and interleukin-1β, thereby participating in the occurrence and development of As. Therefore, specific inhibitors targeting NLRP3 inflammasome and downstream inflammatory factors are potential targets for current clinical drug research and are expected to be a new therapeutic measure for treating As. In this article, the mechanism of NLRP3 inflammasome and the relationship with As are discussed, and drugs targeting NLRP3 inflammasome and downstream inflammatory factors are also described.

Abstract:T-cadherin (T-cad) is a newly discovered adiponectin receptor, which can bind to adiponectin hexamer and high molecular weight polymer. T-cad is widely expressed in many tissues in vivo, especially in the cardiovascular system. T-cad is closely related to coronary heart disease, and has the effects of inhibiting cell apoptosis, preventing atherosclerosis, limiting vascular intimal hyperplasia, inducing vascular endothelial cell proliferation, promoting the secretion of growth factors, and promoting muscle regeneration. Therefore, exploring the mechanism of T-cad in coronary heart disease may provide new ideas for the diagnosis and treatment of coronary heart disease.