Organelle damage is a significant contributor to myocardial ischemia/reperfusion (I/R) injury. This damage often leads to disruption of endoplasmic reticulum protein regulatory programs and dysfunction of mitochondrial energy metabolism. Mitochondria and endoplasmic reticulum are seamlessly connected through the mitochondrial-associated endoplasmic reticulum membrane (MAM), which serves as a crucial site for the exchange of organelles and metabolites. However, there is a lack of reports regarding the communication of information and metabolites between mitochondria and related organelles, which is a crucial factor in triggering myocardial I/R damage. To address this research gap, this review described the role of crosstalk between mitochondria and the correlative organelles such as endoplasmic reticulum, lysosomal and nuclei involved in reperfusion injury of the heart. In summary, this review aims to provide a comprehensive understanding of the crosstalk between organelles in myocardial I/R injury, with the ultimate goal of facilitating the development of targeted therapies based on this knowledge.
Aim To investigate the mechanism and signal pathways of xeroderma pigmentosum group D(XPD)gene on the proliferation of human umbilical vein smooth muscle cell(HUVSMC)induced by ox-LDL.Methods HUVSMCs were transfected with the plasmids of pEGFP-N2/XPD using Lipofectamine 2000,and subsequently silent mTOR gene.MTT and EdU assay was used to detect the cell proliferation.Flow cytometry was used to examine the cell apoptosis.The expression of XPD,lectin-like oxidized low-density lipoprotein receptor 1(LOX-1),mTOR,phospho-mTOR,Bcl-2 and Bax was measured by Western blot.Results The expression of XPD and Bax protein was down-regulated in ox-LDL group(P＜0.05),while the expression of LOX-1,mTOR,Bcl-2 protein and the ratio of Bcl-2/Bax was significantly up-regulated(P＜O.05),compared with control group.Cell proliferation of ox-LDL group increased ob-viously(P＜0.05).After transfected with the pEGFP-N2/XPD plasmid,the expression of Bax was significantly up-regu-lated,while the expression of LOX-1,mTOR,Bcl-2 and the ratio of Bcl-2/Bax were significantly down-regulated(P＜0.05).Flow cytometry showed that overexpression of XPD increased the apoptosis rate of HUVSMC(P＜0.05).MTT and BdU showed that cell proliferation of pEGFP-N2/XPD group reduced compared with control group(P＜0.05).Com-pared with control group,the expression of LOX-1 was significantly down-regulated in siRNA mTOR group(P＜0.05).Conclusion XPD can inhibit HUVSMC proliferation and promote its apoptosis,and reduce the effect of ox-LDL promoting proliferation of HUVSMC via the mTOR/LOX-1 pathway.XPD may be the target of treatment of atherosclerosis.
Aim To explore the correlation between protein tyrosine kinase 7(PTK7)and coronary heart disease(CHD)and its diagnostic value.Methods Target genes were obtained through the Gene Expression Omnibus(GEO)database.StataSE15 was used to find the total standardized mean difference(SMD)of PTK7 and plot the sum-mary receiver operating characteristic(SROC)curve.Next,reverse transcription quantitative polymerase chain reaction was used to verify the expression of PTK7 in CHD and non-CHD population samples and search for CHD-related single-cell RNA sequencing data from GEO to analyze the expression of PTK7 in different cells.The upstream transcription factor(TF)of PTK7 was predicted by the Cistrome Data Browser database.Moreover,enrichment analysis of the gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)were performed on the differentially co-expressed genes.Results By calculating the SMD of PTK7,it was found that PTK7 was highly expressed in the peripheral blood leukocytes(PBL)of patients with CHD(total SMD=0.81,95％confidence interval=0.17～1.45).The population sample vali-dation confirmed the above results.When SROC was plotted,the area under the curve(AUC)was 0.79,indicating that PTK7 has the ability to distinguish between CHD and non-CHD.The single-cell RNA sequencing results showed that the expression ratio of PTK7 was relatively low in different cells of normal peripheral blood.In addition,potential upstream TFs of PTK7 were predicted through the ChIP-seq database,where it was found that IRAKI,SNAI2 may be positive up-stream TFs of PTK7,and EP300,NIPBL may be negative upstream TFs of PTK7.Conclusion Highly expressed PTK7 in PBL is positively correlated with the pathogenesis of CHD,demonstrating that PTK7 has definite diagnostic value on CHD.
Aim To screen the early and advanced atherosclerosis differential genes associated with cuproptosis by bioinformatic methods,and analyze their mechanisms of action,and predict potential biomarkers.Methods The information related to early and advanced atherosclerosis(GSE28829 and GSE43292 data sets)was downloaded from GEO database and standardized.19 cuproptosis genes were obtained from the literature.Difference analysis,enrichment a-nalysis,consensus clustering algorithm,principal component analysis,immune cell infiltration and screening core genes were used to find their action mechanisms and potential biomarkers.Results Finally,10 differential genes related to cuproptosis were screened.The correlation analysis of differential genes related to cuproptosis showed a strong positive correlation between GLS and DBT(r=0.78,P＜0.001),while NLRP3 showed a strong negative correlation with DBT and GLS(r=-0.62,P＜0.001).GO enrichment analysis of differential genes related to cuproptosis was mainly related to copper ion transport and copper homeostasis,and KEGG analysis showed that it was mainly enriched in platinum resist-ance,mineral absorption and central carbon metabolic pathway in cancer.The PPI network analysis and MCODE were used to screen core genes.The results of immune cell infiltration showed that M2 macrophages,M0 macrophages,resting CD4 memory T cells,and CD8+T cells were dominant(P＜0.05).The correlation analysis of differential genes related to immune cells and cuproptosis showed that in the early stage of atherosclerosis,GLS was strongly positively correlated with activated NK cells(r=0.52,P＜0.001),FDX1 and SLC31A1 was strongestly negatively correlated with CD8+T cells(r=-0.51,P＜0.001);in the advanced stage of atherosclerosis,FDX1 was strongestly positively correlated with M0 macro-phages(r=0.58,P＜0.001)and FDX1 was strongestly negatively correlated with CD8+T cells(r=-0.55,P＜0.001).Principal component analysis showed that two subtypes Cl and C2 could be clearly distinguished according to the expression of cuproptosis-related differential genes.Conclusion The immune-related changes between cuproptosis and the devel-opment of atherosclerosis may be the key to the diagnosis and treatment of early and advanced atherosclerosis,and the core genes SLC31A1,MTF1,ATP7B and ATP7A may be potential markers and therapeutic targets for the development of ather-osclerosis.
Aim To construct a nomogram model for predicting the risk of coronary artery calcification in patients with chronic obstructive pulmonary disease(COPD)and evaluate its predictive efficiency.Methods The data of DRYAD database were analyzed by the R software.Multivariate Logistic regression analysis was used to screen in-dependent predictors of coronary artery calcification risk in patients with COPD,and a personalized nomogram prediction model was constructed.Receiver operating characteristic(ROC)curve was used to evaluate the predictive effect of the nomogram model.Results Multivariate Logistic regression analysis showed that male,advanced age,use of statins and use of ACE inhibitors or ARB antihypertensive drugs were independent risk factors for coronary artery calcification in COPD patients(P＜0.05).The area under the ROC curve(AUC)of the constructed nomogram model was 0.779,95％CI:0.725～0.834,suggesting that the nomogram had good discrimination.The Hosmer-Lemeshow goodness-of-fit test showed that there was no significant difference between the predicted probability of nomogram and the actual frequency of coronary artery calcification(x2=6.240,P=0.621),that is,the nomogram model had good calibration.The DCA curve showed that when the threshold probability of coronary artery calcification in COPD patients was between 0.26 and 0.96,the net benefit of patients using the nomogram model was significantly better than that of the"full intervention"and"no intervention measures,suggesting that the nomogram model has good clinical applicability.Conclusion The nomogram prediction model constructed in this study can be used to assist clinical staff to screen out COPD populations with high risk of coronary calcification,formulate individualized targeted intervention plans,and reduce the incidence of coronary calcification in COPD patients.
Aim To explore the role of circular RNA spindle and kinetochore-associated protein 3(circ-SKA3)in regulating Toll-like receptor 4(TLR4)axis in atherosclerosis(As)through miR-1303.Methods Carotid artery plaque,diseased vascular tissue,normal tissue adjacent to plaque and venous blood were collected from 30 patients with As treated by carotid endarterectomy from April 2019 to April 2022.Another 30 normal venous blood samples were collected.Microarray analysis,quantitative real-time polymerase chain reaction(qRT-PCR)and fluorescence in situ hy-bridization(FISH)were used to detect the expression and localization of circ-SKA3 in plaque tissue of As patients,control samples,plasma exosome,human umbilical vein endothelial cell(HUVEC)and aorta of As model mice.The relationship among circ-SKA3,miR-1303 and TLR4 was verified by bioinformatics,double luciferase reporter gene detection and RNA immunoprecipitation.The proliferation,migration and angiogenesis of HUVEC were detected by CCK-8,scratch,Transwell and angiogenesis experiments.TLR4 axis-related protein expression was detected by Western blot-ting.Pathological changes of aorta in As model mice was observed by Oil red O staining,HE staining and Masson stai-ning.TLR4 expression in aorta of As model mice was detected by immunohistochemistry and immunofluorescence.Results The expression levels of circ-SKA3 and TLR4 in plaque tissue,plasma exosome,oxidized low density lipoprotein(ox-LDL)treated HUVEC and circ-SKA3,TLR4 in aortic of As model mice were up-regulated(P＜0.05),while the ex-pression level of miR-1303 was down-regulated(P＜0.05).Functional analysis showed that circ-SKA3 promoted HUVEC damage in vitro and As progress in vivo.Mechanism analysis showed that circ-SKA3 could promote TLR4 expression by adsorbing miR-1303 by sponge.Inhibition of circ-SKA3/miR-1303/TLR4 axis can inhibit the formation of As lesions.Conclusions circ-SKA3 is overexpressed in carotid plaque,plasma exosome,ox-LDL-treated HUVEC and As model mouse aorta in As patients.circ-SKA3/miR-1303/TLR4 axis can promote the development of As model in vivo and in vitro.
Aim To analyze the incidence and influencing factors of coronary artery calcification(CAC)by low dose chest CT in asymptomatic middle-aged male patients,and to explore the value of low dose chest CT in early screening of cardiovascular diseases.Methods 2 571 asymptomatic male participants aged 40～65 were selected who underwent health examination at General Hospital of Eastern Theater Command from January to December 2022.General data,blood indicators,chest CT and other data were collected,and participants were divided into CAC group(n=422)and non-CAC group(n=2 149)according to whether chest CT indicated CAC.The differences between the two groups and the risk fac-tors of CAC were analyzed.Results Among 2 571 asymptomatic middle-aged male patients,the positive rate of CAC was 16.41％.The age,body mass index(BMI),systolic blood pressure,diastolic blood pressure,pulse,waist circum-ference,alanine aminotransferase(ALT),aspartate aminotransferase(AST),blood urea nitrogen(BUN),triglycerides(TG),fasting blood glucose(FBG),and glycated hemoglobin(HbAlc)were higher in CAC group than in non-CAC group,and the red blood cell count(RBC)was lower in CAC group than that in non-CAC group(all P＜0.05).Univari-ate Logistic regression analysis showed that the effects of age,BMI,systolic blood pressure,diastolic blood pressure,pulse,waist circumference,RBC,ALT,AST,BUN,TG,FBG,and HbAlc on CAC were statistically significant(all P＜0.05).Multivariate Logistic regression analysis showed that age,BMI,diastolic blood pressure,RBC,and AST were in-dependent risk factors for CAC(all P＜0.05).Conclusion Age,BMI,diastolic blood pressure,RBC,and AST are independent risk factors for CAC in low dose chest CT,and physical examination chest CT is valuable in cardiovascular dis-ease screening.
Artery stenosis due to atherosclerosis is the most common cause of cardiovascular disease.In addition to known risk factors,researchers have found that intestinal flora can influence the pathogenesis of atherosclerosis through its metabolites(short-chain fatty acids,trimethylamine oxide,indoles),the metabolism of bile acids,and the inflammatory response,and the relevant evidence has been supported experimentally.This article presents a systematic review of the relationship between intestinal flora and atherosclerotic cardiovascular disease,the microscopic mechanisms by which intes-tinal flora affect the pathogenesis of atherosclerotic cardiovascular disease,and recent advances in the treatment of athero-sclerotic cardiovascular disease using intestinal flora as a target.
Atherosclerosis is the leading cause of cardiovascular and cerebrovascular diseases caused by smoking,hypertension,aging,obesity,circadian clock disorders,and other factors.As a molecular machine for protein synthesis,ribosomes maintain protein homeostasis in cells.This review focuses on the impact of aging,obesity,and circadian clock disorders on the development of atherosclerosis and the relationship with ribosome biogenesis and provides the theoretical basis for both basic research and clinical intervention of atherosclerosis.
With the deepening understanding of hypertension,more and more evidence suggests that the blood pres-sure levels of hypertensive patients are closely related to sodium salts.The gut microbiome is made up of bacteria,ar-chaea,fungi,protozoa and viruses,also known as the gut microbiome,intestinal flora and its metabolites,as a hot re-search direction in hypertension,play an important role in the relationship between sodium and blood pressure.Excessive sodium salt can change the type and proportion of intestinal microbiota,affect the level of inflammation and metabolism of the body and accelerate the occurrence and development of hypertension.Sodium control is a low-cost and effective way to control blood pressure.This article reviews the complex relationship between sodium salts,gut microbiota,and hyperten-sion,hoping to provide theoretical support for the prevention,treatment,and control of hypertension.
Acute myocardial infarction(AMI)is one of the main causes of death from cardiovascular and cerebro-vascular diseases worldwide.Rapid and efficient diagnosis of AMI plays an important role in the treatment and prognosis of the disease.Studies suggest that microRNA(miRNA)may be an important molecular marker for the diagnosis of AMI and provide directions for AMI treatment.This review summarizes the feasibility of miRNA as a diagnostic marker for AMI,its effect on AMI and its related molecular mechanisms.
Cardiopulmonary function is a powerful indicator of overall health and cardiovascular or all-cause mortali-ty.Exercise is an important non-pharmacological treatment modality in the prevention and management of hypertension,primarily including continuous aerobic exercise,high-intensity interval training,and resistance exercise.Different exercise patterns not only contribute to blood pressure reduction in hypertensive patients,but also effectively improve car-diopulmonary function.This article provides a review of the impact of various exercise modalities,particularly aerobic ex-ercise,on the cardiopulmonary function of hypertensive patients,aiming to offer assistance in formulating scientific exercise intervention strategies for individuals with hypertension.
[目的]采用GEO数据库探讨痛风合并动脉粥样硬化(As)的共同发病机制.[方法]从GEO数据库中下载痛风(GSE160170)和As(GSE100927)的基因表达矩阵,分析痛风和As的差异表达基因(DEG),并分别进行富集分析.在分析共同差异表达基因(CDEG)后,对其进行功能富集分析、蛋白质-蛋白质相互作用(PPI)网络分析和核心基因(HG)鉴定,并对HG进行共表达分析及验证.最后,分析痛风、As的免疫细胞浸润,同时探索HG与浸润免疫细胞(IIC)之间的相关性.[结果]GSE160170数据集中获得了 1 606个DEG,GSE100927数据集中获得了 481个DEG.其中的22个CDEG富集分析结果表明,细胞因子的调控作用可能是痛风合并As的关键机制.通过使用 CytoHubba 插件识别了 6 个 HG(CCR2、CD2、FCGR3A、FGD3、IL10RA、SIGLEC1),结果显示这些 HG 尚且可靠.共表达网络显示这些HG可以影响肿瘤坏死因子超家族细胞因子产生的调节作用.免疫细胞浸润分析表明,痛风中的NK细胞表达显著增加,且与CCR2基因呈显著相关;As中的活化肥大细胞表达显著增加,且与CD2基因呈显著相关.[结论]肿瘤坏死因子超家族细胞因子产生的调节作用很可能是痛风合并As的核心因素.
氧化三甲胺是肠道菌群的代谢产物之一,通过多条信号通路影响冠状动脉粥样硬化性疾病的病理过程,具有促进血管内皮细胞损伤、参与血管壁脂质沉积、促进炎症发生发展并刺激平滑肌细胞衰老、迁移等作用.研究表明,通过介导氧化三甲胺的代谢及相关信号通路的激活,可以预防并治疗动脉粥样硬化性疾病.文章将围绕氧化三甲胺参与动脉粥样硬化的作用机制进行简要综述,以期为动脉粥样硬化性疾病的防治提供新的研究思路.
[目的]研究致心律失常型右心室心肌病(ARVC)患者冠状动脉狭窄对心脏病理和心肌代谢组学的影响.[方法]取35例接受心脏移植的ARVC患者受体心脏冠状动脉和心室6个部位(左心室前壁、侧壁、后壁以及右心室前壁、后壁、室间隔),冠状动脉组织切片行HE染色,并定量分析其狭窄程度;心室组织切片行Masson染色,经图像处理后定量分析心脏组织中心肌、纤维、脂肪成分所占比例.冠状动脉供血区域心脏组织进行代谢物提取及代谢组学分析.无冠状动脉狭窄组、轻度冠状动脉狭窄(＜50％)组、中重度冠状动脉狭窄(≥50％)组的心脏组织中心肌、纤维、脂肪成分的差异和代谢物差异进行对比分析.[结果]35例ARVC患者中,中重度冠状动脉狭窄患者10例(28.6％),轻度冠状动脉狭窄患者11例(31.4％),无冠状动脉狭窄患者14例(40.0％).中重度冠状动脉狭窄患者接受心脏移植的年龄显著高于轻度冠状动脉狭窄患者和无冠状动脉狭窄患者[(48.5±10.7)岁比(33.8±10.5)岁和(31.0±13.4)岁,P=0.015].中重度、轻度冠状动脉狭窄患者和无冠状动脉狭窄患者的心肌、纤维、脂肪成分所占比例在左心室前壁、侧壁、后壁和右心室前壁、后壁、室间隔6个部位的差异均无统计学意义(P＞0.05).代谢组学检测发现105种代谢物,集中于三羧酸循环、氨基酸代谢、嘌呤代谢、嘧啶代谢、戊糖磷酸代谢及糖酵解糖异生代谢等通路,与无狭窄冠状动脉供血区心肌组织相比,中重度、轻度狭窄冠状动脉供血区心肌组织中没有显著上调或下调的代谢产物.主成分分析和热图分析表明三组之间的代谢谱无显著差异(P＞0.05).[结论]在ARVC患者中,中重度、轻度冠状动脉狭窄与无冠状动脉狭窄者的心脏组织中心肌、纤维、脂肪所占比例无明显组间差异,代谢组学检测亦无明显组间差异.
[目的]探讨准分子激光斑块消蚀术(ELA)治疗膝下动脉粥样硬化闭塞症的临床疗效及安全性,以期为膝下动脉硬化闭塞症患者腔内治疗方案提供更多选择.[方法]回顾性收集2019年12月-2021年12月新疆维吾尔自治区人民医院血管外科收治的50例(计50条肢体)膝下动脉硬化闭塞症患者的临床资料,按照治疗方法的不同分为ELA组(n=25)和普通球囊扩张术(POBA)组(n=25),比较两组患者的临床特征、围术期有无严重手术并发症、靶血管术后随访期间一期通畅率、术后踝臂指数(ABI)改善情况、视觉模拟量表(VAS)评分、保肢(趾)率.[结果]两组手术成功率均为100％,围术期均无严重并发症,两组患者治疗后ABI和VAS较治疗前均显著改善,且术后3天、术后6月ELA组ABI高于POBA组,差异有统计学意义(P＜0.05);术后6月ELA组VAS评分低于POBA组,差异有统计学意义(P＜0.05);随访期内ELA组一期通畅率及保肢(趾)率均高于POBA组(P＜0.05).[结论]ELA治疗膝下动脉硬化闭塞症是安全可行的,且初步显示近期疗效优于POBA,为膝下动脉病变腔内治疗提供了更多的选择.
[目的]探讨颅脑CT灌注(CTP)成像对重度颈动脉狭窄(CAS)患者保守治疗的反应性评估价值.[方法]选取重度CAS患者90例作为研究对象,均接受保守治疗,根据1年内是否出现脑缺血性疾病分为低反应组和高反应组.对比两组局部脑血容量(rCBV)、局部脑血流量(rCBF)、局部平均通过时间(rMTT)、局部达峰时间(rTTP),采用Cox回归模型分析保守治疗反应性的独立危险因素,列线图分析rCBV、rCBF、rTTP、rMTT对保守治疗反应性的评估价值,并进行决策曲线及临床影响曲线验证.[结果]随访1年,90例重度CAS患者脱落2例,有效随访88例,未发生脑缺血相关并发症65例(高反应组),发生脑缺血性疾病23例(低反应组),其中短暂性脑缺血发作15例(17.05％),脑梗死8例(9.09％);治疗3个月,两组rCBF大于治疗前,rMTT、rTTP小于治疗前(P＜0.05);治疗前和治疗3个月,低反应组rCBF小于高反应组,rMTT、rTTP大于高反应组(P＜0.05);应用Cox回归模型筛选出的收缩压、尿酸、rCBF、rMTT、rTTP构建重度CAS患者保守治疗反应性列线图预测模型,一致性指数为0.896;校正曲线分析显示,预测模型预测保守治疗反应性与实际保守治疗反应性吻合度较高;在阈值为0.16～0.95范围内,列线图模型联合评估重度CAS患者保守治疗反应性的净受益率优于单独检测;在阈值概率为0.41时,被联合检测方案划分为高风险的人数与真阳性例数基本达到一致.[结论]CTP成像参数与重度CAS患者治疗反应性关系密切,可为临床早期评估治疗反应性提供参考,有助于确保患者获益.
动脉粥样硬化是心血管疾病导致死亡的最主要原因之一,但其发病原因还没有完全清楚,其防治方法有限.冠状血管是最容易发生动脉粥样硬化的血管,其相应的解剖也有特殊意义,本文就冠状血管的解剖、动脉粥样硬化的靶向治疗及动脉粥样硬化并发症的治疗进行述评.
Multiple factors cause atherosclerosis， and its pathogenesis is complex and has not been fully elucidated. Polyunsaturated fatty acids， a member of the fatty acid family， are critical nutrients for mammalian growth and development. Types and intakes of polyunsaturated fatty acids， and fatty acid desaturase can affect the course of atherosclerotic disease. Fatty acid desaturase gene cluster can regulate fatty acid desaturase activity and further affect atherosclerosis. Based on the metabolic and genetics perspectives， this study reviewed the research progress on the effects of polyunsaturated fatty acids on atherosclerosis regulated by fatty acid desaturase and the relationship between genetic variants of the fatty acid desaturase gene cluster and atherosclerotic cardiovascular disease was summarized.
[目的]观察急性心肌梗死(AMI)患者治疗前后心室重构相关指标的变化及药物不良反应情况,评价不同剂量沙库巴曲缬沙坦治疗AMI后心力衰竭患者的疗效及安全性.[方法]选取2018年3月-2022年3月的174例急性ST段抬高型心肌梗死(STEMI)合并左心室射血分数(LVEF)＜50％的患者按随机分配接受最大耐受剂量的沙库巴曲缬沙坦(滴定至200 mg或最大耐受剂量,Bid,n=80)或低剂量沙库巴曲缬沙坦(50 mg,Bid,n=94)治疗,同时接受常规治疗.评价患者从基线检查(治疗前)至出院后12个月的血清氨基末端脑钠肽前体(NT-proBNP)、超声心动图各参数及药物不良反应(症状性低血压、高钾血症、肾功能下降、血管性水肿等)的变化.[结果]经治疗后最大耐受剂量组与低剂量组左心房内径(LAD)对比治疗前差异均有统计学意义(P＜0.05),但两组间差异无统计学意义(P＞0.05);两组左心室舒张期末内径(LVEDD)与治疗前比较均显著下降(P＜0.05),但两组间差异无统计学意义(P＞0.05);两组左心室射血分数(LVEF)与治疗前比较均显著升高(P＜0.05),程度相似(P＞0.05);最大耐受剂量组血清NT-proBNP水平下降幅度高于低剂量组,差异有统计学意义(P＜0.05);最大耐受量组药物相关不良反应发生率更高(17.5％比2.1％,P＜0.05).[结论]与低剂量组相比,最大耐受剂量组在改善心肌梗死后心力衰竭患者心脏重构和左心室射血功能上并没有显示出显著优势,虽然可能通过进一步降低NT-proBNP水平减少心血管事件发生,但严格滴定最大耐受剂量与频繁发生药物不良反应密切相关.
