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.
