Cardiovascular Therapeutics最新文献

{"title":"Bardoxolone Methyl Ameliorates Myocardial Ischemia/Reperfusion Injury by Activating the Nrf2/HO-1 Signaling Pathway.","authors":"Anwu Huang, Zhaolin Wang, Hua Tang, Zhuyin Jia, Xiaojun Ji, Xuehua Yang, Wenbing Jiang","doi":"10.1155/2023/5693732","DOIUrl":"10.1155/2023/5693732","url":null,"abstract":"<p><strong>Background: </strong>Myocardial ischemia/reperfusion (I/R) injury is a severe heart problem resulting from restoring coronary blood flow to the myocardium after ischemia. This study is aimed at ascertaining the therapeutic efficiency and action mechanism of bardoxolone methyl (BARD) in myocardial I/R injury.</p><p><strong>Methods: </strong>In male rats, myocardial ischemia was performed for 0.5 h, and then, reperfusion lasted for 24 h. BARD was administrated in the treatment group. The animal's cardiac function was measured. Myocardial I/R injury serum markers were detected via ELISA. The 2,3,5-triphenyltetrazolium chloride (TTC) staining was used to estimate the infarction. H&E staining was used to evaluate the cardiomyocyte damage, and Masson trichrome staining was used to observe the proliferation of collagen fiber. The apoptotic level was assessed via the caspase-3 immunochemistry and TUNEL staining. Oxidative stress was measured through malondialdehyde, 8-hydroxy-2'-deoxyguanosine, superoxide dismutase, and inducible nitric oxide synthases. The alteration of the Nrf2/HO-1 pathway was confirmed via western blot, immunochemistry, and PCR analysis.</p><p><strong>Results: </strong>The protective effect of BARD on myocardial I/R injury was observed. In detail, BARD decreased cardiac injuries, reduced cardiomyocyte apoptosis, and inhibited oxidative stress. For mechanisms, BARD treatment significantly activates the Nrf2/HO-1 pathway.</p><p><strong>Conclusion: </strong>BARD ameliorates myocardial I/R injury by inhibiting oxidative stress and cardiomyocyte apoptosis via activating the Nrf2/HO-1 pathway.</p>","PeriodicalId":9582,"journal":{"name":"Cardiovascular Therapeutics","volume":"2023 ","pages":"5693732"},"PeriodicalIF":3.4,"publicationDate":"2023-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9977528/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9394359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Updated Meta-Analysis for Safety Evaluation of Alirocumab and Evolocumab as PCSK9 Inhibitors.","authors":"Hye Duck Choi, Ji Hae Kim","doi":"10.1155/2023/7362551","DOIUrl":"10.1155/2023/7362551","url":null,"abstract":"<p><strong>Background: </strong>Alirocumab and evolocumab, as protein convertase subtilisin kexin type 9 (PCSK9) inhibitors, have been reported to reduce cardiovascular risk. This meta-analysis is aimed at updating the safety data of PCSK9 inhibitors.</p><p><strong>Methods: </strong>We assessed the relative risk for all treatment-related adverse events, serious adverse events, diabetes-related adverse events, and neurocognitive and neurologic adverse events with PCSK9 inhibitors compared to controls (placebo or ezetimibe). In addition, we conducted a meta-analysis to quantitatively integrate and estimate the adverse event rates in long-term studies.</p><p><strong>Results: </strong>There were no significant differences between PCSK9 inhibitors and controls in the relative risk analysis. In a subgroup analysis of each PCSK9 inhibitor, alirocumab treatment significantly reduced the risk of serious adverse events compared to control treatment (risk ratio (RR) = 0.937; 95% confidence interval (CI), 0.896-0.980), but no significant difference was observed with evolocumab treatment (RR = 1.003; 95% CI, 0.963-1.054). Moreover, alirocumab treatment afforded a significant reduction in the risk of diabetes-related adverse events compared to control treatment (RR = 0.9137; 95% CI, 0.845-0.987). The overall incidence (event rate) of long-term adverse events was 75.1% (95% CI, 71.2%-78.7%), and the incidence of serious long-term event rate was 16.2% (95% CI, 11.6%-22.3%).</p><p><strong>Conclusions: </strong>We suggest that alirocumab and evolocumab are generally safe and well tolerated and that their addition to background lipid-lowering therapy is not associated with an increased risk of adverse events or toxicity.</p>","PeriodicalId":9582,"journal":{"name":"Cardiovascular Therapeutics","volume":"2023 ","pages":"7362551"},"PeriodicalIF":3.4,"publicationDate":"2023-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9834631/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9142906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacological Activation of Rev-erb<i>α</i> Attenuates Doxorubicin-Induced Cardiotoxicity by PGC-1<i>α</i> Signaling Pathway.","authors":"Runmei Zou,&nbsp;Shuo Wang,&nbsp;Hong Cai,&nbsp;Yuwen Wang,&nbsp;Cheng Wang","doi":"10.1155/2023/2108584","DOIUrl":"https://doi.org/10.1155/2023/2108584","url":null,"abstract":"<p><strong>Background: </strong>Doxorubicin-induced cardiotoxicity has been closely concerned in clinical practice. Rev-erb<i>α</i> is a transcriptional repressor that emerges as a drug target for heart diseases recently. This study is aimed at investigating the role and mechanism of Rev-erb<i>α</i> in doxorubicin-induced cardiotoxicity.</p><p><strong>Methods: </strong>H9c2 cells were treated with 1.5 <i>μ</i>M doxorubicin, and C57BL/6 mice were treated with a 20 mg/kg cumulative dose of doxorubicin to construct doxorubicin-induced cardiotoxicity models in vitro and in vivo. Agonist SR9009 was used to activate Rev-erb<i>α</i>. PGC-1<i>α</i> expression level was downregulated by specific siRNA in H9c2 cells. Cell apoptosis, cardiomyocyte morphology, mitochondrial function, oxidative stress, and signaling pathways were measured.</p><p><strong>Results: </strong>SR9009 alleviated doxorubicin-induced cell apoptosis, morphological disorder, mitochondrial dysfunction, and oxidative stress in H9c2 cells and C57BL/6 mice. Meanwhile, PGC-1<i>α</i> and downstream signaling NRF1, TAFM, and UCP2 expression levels were preserved by SR9009 in doxorubicin-treated cardiomyocytes in vitro and in vivo. When downregulating PGC-1<i>α</i> expression level by specific siRNA, the protective role of SR9009 in doxorubicin-treated cardiomyocytes was attenuated with increased cell apoptosis, mitochondrial dysfunction, and oxidative stress.</p><p><strong>Conclusion: </strong>Pharmacological activation of Rev-erb<i>α</i> by SR9009 could attenuate doxorubicin-induced cardiotoxicity through preservation of mitochondrial function and alleviation of apoptosis and oxidative stress. The mechanism is associated with the activation of PGC-1<i>α</i> signaling pathways, suggesting that PGC-1<i>α</i> signaling is a mechanism for the protective effect of Rev-erb<i>α</i> against doxorubicin-induced cardiotoxicity.</p>","PeriodicalId":9582,"journal":{"name":"Cardiovascular Therapeutics","volume":"2023 ","pages":"2108584"},"PeriodicalIF":3.1,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9977526/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9411579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elevated Serum Total Bilirubin Might Indicate Poor Coronary Conditions for Unstable Angina Pectoris Patients beyond as a Cardiovascular Protector.","authors":"Qi Liang,&nbsp;Yongjian Zhang,&nbsp;Jin Liang","doi":"10.1155/2023/5532917","DOIUrl":"https://doi.org/10.1155/2023/5532917","url":null,"abstract":"<p><strong>Backgrounds: </strong>Serum total bilirubin (STB) is recently more regarded as an antioxidant with vascular protective effects. However, we noticed that elevated STB appeared in unstable angina pectoris (UAP) patients with diffused coronary lesions. We aimed to explore STB's roles in UAP patients, which have not been reported by articles.</p><p><strong>Methods and results: </strong>1120 UAP patients were retrospectively screened, and 296 patients were finally enrolled. They were grouped by Canadian Cardiovascular Society (CCS) angina grades. The synergy between PCI with TAXUS stent and cardiac surgery score (SYNTAX score) and corrected thrombolysis in myocardial infarction flow count (CTFC) were adopted to profile coronary features. The results showed that STB, mean platelet volume (MPV), hs-CRP, fasting blood glucose (FBG), red blood cell width (RDW), and CTFC elevated significantly in the CCS high-risk group. STB (<i>B</i> = 0.59, 95% CI: 0.39-0.74, <i>P</i> < 0.01) and MPV (<i>B</i> = 0.86, 95% CI: 0.42-1.31, <i>P</i> < 0.01) could indicate SYNTAX score changes for these patients. STB (≥21.7 <i>μ</i>mol/L) could even indicate a coronary slow flow condition (AUC: 0.88, 95% CI: 0.84-0.93, <i>P</i> < 0.01). Moreover, UAP patients with elevated STB had a lower event-free survival rate by the Kaplan-Meier curve. STB ≥21.7 <i>μ</i>mol/L could reflect a poor coronary flow status and indicate 1-year poor outcomes for these patients (HR: 2.01, 95% CI: 1.06-3.84, <i>P</i> < 0.01).</p><p><strong>Conclusion: </strong>Elevated STB in UAP patients has a close relationship with changes in SYNTAX score. STB (over 21.7 <i>μ</i>mol/L) could even indicate a coronary slow flow condition and poor outcomes for the UAP patients.</p>","PeriodicalId":9582,"journal":{"name":"Cardiovascular Therapeutics","volume":"2023 ","pages":"5532917"},"PeriodicalIF":3.1,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10497366/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10260120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of Potential Biomarkers for Coronary Artery Disease Based on Cuproptosis.","authors":"Bohong Zhang,&nbsp;Mingliang He","doi":"10.1155/2023/5996144","DOIUrl":"https://doi.org/10.1155/2023/5996144","url":null,"abstract":"<p><p>Identifying peripheral biomarkers is an important noninvasive diagnosis method for coronary artery disease (CAD) which has aroused the strong interest of researchers. Cuproptosis, a newly reported kind of programmed cell death, is closely related to mitochondrial respiration, adenosine triphosphate (ATP) production, and the TCA cycle. Currently, no studies have been published about the effects of cuproptosis-related genes (CRGs) on diagnosing CAD. To screen marker genes for CAD from CRGs, we downloaded the whole blood cell gene expression profile of CAD patients and normal samples, i.e., the GSE20680 dataset, from the GEO database. By differential expression analysis, we obtained 10 differentially expressed CRGs (DE-CRGs), which were associated with copper ion response, immune response, and material metabolism. Based on the 10 DE-CRGs, we furtherly performed LASSO analysis and SVM-RFE analysis and identified 5 DE-CRGs as marker genes, including F5, MT4, RNF7, S100A12, and SORD, which had an excellent diagnostic performance. Moreover, the expression of the marker genes was validated in the GSE20681 and GSE42148 datasets, and consistent results were obtained. In mechanism, we conducted gene set enrichment analyses (GSEA) based on the marker genes, and the results implied that they might participate in the regulation of immune response. Therefore, we calculated the relative contents of 22 kinds of immune cells in CAD and normal samples using the CIBERSORT algorithm, followed by differential analysis and correlation analysis of the immune microenvironment, and found that regulatory T cell (Treg) significantly decreased and was negatively correlated with marker gene S100A12. To further reveal the regulation mechanisms, a lncRNA-miRNA-mRNA ceRNA network based on the marker genes was established. Finally, 13 potential therapeutic drugs targeting 2 marker genes (S100A12 and F5) were identified using the Drug Gene Interaction Database (DGIdb). In summary, our findings indicated that some CRGs may be diagnostic biomarkers and treatment targets for CAD and provided new ideas for further scientific research.</p>","PeriodicalId":9582,"journal":{"name":"Cardiovascular Therapeutics","volume":"2023 ","pages":"5996144"},"PeriodicalIF":3.1,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9891837/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9236832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"KCa3.1 Promotes Proinflammatory Exosome Secretion by Activating AKT/Rab27a in Atrial Myocytes during Rapid Pacing.","authors":"Dishiwen Liu,&nbsp;Huiyu Chen,&nbsp;Yuntao Fu,&nbsp;Yajun Yao,&nbsp;Shanqing He,&nbsp;Youcheng Wang,&nbsp;Zhen Cao,&nbsp;Xuewen Wang,&nbsp;Mei Yang,&nbsp;Qingyan Zhao","doi":"10.1155/2023/3939360","DOIUrl":"https://doi.org/10.1155/2023/3939360","url":null,"abstract":"<p><strong>Purpose: </strong>The aim of this study was to investigate the role of the medium-conductance calcium-activated potassium channel (KCNN4, KCa3.1) in the secretion of proinflammatory exosomes by atrial myocytes.</p><p><strong>Methods: </strong>Eighteen beagles were randomly divided into the sham group (<i>n</i> = 6), pacing group (<i>n</i> = 6), and pacing+TRAM-34 group (<i>n</i> = 6). Electrophysiological data, such as the effective refractory period, atrial fibrillation (AF) induction, and AF duration, were collected by programmed stimulation. Atrial tissues were subjected to hematoxylin and eosin, Masson's trichrome, and immunofluorescence staining. The expression of KCa3.1 and Rab27a was assessed by immunohistochemistry and western blotting. The downstream signaling pathways involved in KCa3.1 were examined by rapid pacing or overexpressing KCNN4 in HL-1 cells.</p><p><strong>Results: </strong>Atrial rapid pacing significantly induced electrical remodeling, inflammation, fibrosis, and exosome secretion in the canine atrium, while TRAM-34 (KCa3.1 blocker) inhibited these changes. Compared with those in control HL-1 cells, the levels of exosome markers and inflammatory factors were increased in pacing HL-1 cells. Furthermore, the levels of CD68 and iNOS in macrophages incubated with exosomes derived from HL-1 cells were higher in the pacing-exo group than in the control group. More importantly, KCa3.1 regulated exosome secretion through the AKT/Rab27a signaling pathway. Similarly, inhibiting the downstream signaling pathway of KCa3.1 significantly inhibited exosome secretion.</p><p><strong>Conclusions: </strong>KCa3.1 promotes proinflammatory exosome secretion through the AKT/Rab27a signaling pathway. Inhibiting the KCa3.1/AKT/Rab27a signaling pathway reduces myocardial tissue structural remodeling in AF.</p>","PeriodicalId":9582,"journal":{"name":"Cardiovascular Therapeutics","volume":"2023 ","pages":"3939360"},"PeriodicalIF":3.1,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10079387/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9642657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Effect of Clinically Indicated Liraglutide on Pericoronary Adipose Tissue in Type 2 Diabetic Patients.","authors":"Irmelin I A Biesenbach,&nbsp;Laurits J Heinsen,&nbsp;Katrine S Overgaard,&nbsp;Thomas R Andersen,&nbsp;Søren Auscher,&nbsp;Kenneth Egstrup","doi":"10.1155/2023/5126825","DOIUrl":"https://doi.org/10.1155/2023/5126825","url":null,"abstract":"<p><p>Vascular inflammation can be detected in the pericoronary adipose tissue (PCAT) by coronary computed tomography angiography (CCTA) attenuation. Treatment with liraglutide is associated with anti-inflammatory effects and reduces cardiovascular risk in diabetic patients. This study is aimed at examining the effect of clinically indicated liraglutide on PCAT attenuation. Asymptomatic patients with type 2 diabetes mellitus (T2DM) and without known ischemic heart disease underwent clinical examination, blood analysis, and CCTA. The main coronary arteries were outlined and PCAT attenuation was measured on the proximal 40 mm. Patients treated with liraglutide on a clinical indication were compared to patients not receiving liraglutide. The study included 190 patients; 53 (28%) received liraglutide (Lira+) and 137 (72%) did not (Lira-). There were no significant differences in PCAT attenuation between the two groups in either artery. However, PCAT attenuation measured around the left anterior descending artery (LAD) was lower in the Lira+ group after adjustment for age, sex, body mass index, and T2DM duration (<i>b</i> coefficient -2.4, <i>p</i> = 0.029). In a population of cardiac asymptomatic T2DM patients, treatment with clinically indicated liraglutide was not associated with differences in PCAT attenuation compared to nonliraglutide treatment in the unadjusted model. An association was seen in the adjusted model for the left anterior descending artery, possibly indicating an anti-inflammatory effect.</p>","PeriodicalId":9582,"journal":{"name":"Cardiovascular Therapeutics","volume":"2023 ","pages":"5126825"},"PeriodicalIF":3.1,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9867582/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10277785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of Statins on Major Adverse Cardiovascular Events in Patients with Coronary Artery Spasm: A Meta-Analysis of the Asia Region.","authors":"Tian-Jun Zhao,&nbsp;Duan Luo,&nbsp;Xi Jiang,&nbsp;Feng Tang,&nbsp;Hui Jiang","doi":"10.1155/2023/8807278","DOIUrl":"https://doi.org/10.1155/2023/8807278","url":null,"abstract":"<p><strong>Background: </strong>Whether statins can reduce major cardiovascular adverse events (MACE) in patients with coronary artery spasm (CAS) is controversial. And most of the relevant research to date has been conducted in Asia.</p><p><strong>Methods: </strong>We systematically searched electronic databases for studies on the effect of statins on MACE in patients with CAS in Asia and published up to September 2022. We included data on MACE in a statin therapy patient group and a no-statin therapy control group. We then evaluated the effect of statin therapy on MACE in patients with CAS in Asia by meta-analysis and trial sequential analysis (TSA). All statistical analyses were performed using Stata 16.0 software and TSA software.</p><p><strong>Results: </strong>A total of 10 studies (<i>n</i> = 9333 patients) were included in the final analysis. Meta-analysis showed that the use of statins had a significant effect on MACE in CAS patients (with RR, 0.70; 95% CI, 0.49-0.99), and the sensitivity analysis further confirmed this finding. Subgroup analysis suggested that the correlation between statin therapy and reduced MACE endpoint was stronger in Japanese patients and patients followed up for more than 4 years. But our TSA results indicated that the available samples were insufficient and further research is needed.</p><p><strong>Conclusions: </strong>Our meta-analysis suggests that statin therapy can reduce MACE in patients with CAS in Asia, and the correlation between the two was stronger in Japanese patients and patients followed up for more than 4 years.</p>","PeriodicalId":9582,"journal":{"name":"Cardiovascular Therapeutics","volume":"2023 ","pages":"8807278"},"PeriodicalIF":3.1,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10159740/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9805640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Regulation Network of Glycerolipid Metabolism as Coregulators of Immunotherapy-Related Myocarditis.","authors":"Xiguang Yang,&nbsp;Xiaopeng Duan,&nbsp;Zhenglin Xia,&nbsp;Rui Huang,&nbsp;Ke He,&nbsp;Guoan Xiang","doi":"10.1155/2023/8774971","DOIUrl":"https://doi.org/10.1155/2023/8774971","url":null,"abstract":"<p><strong>Background: </strong>To date, immunotherapy for patients with malignant tumors has shown a significant association with myocarditis. However, the mechanism of metabolic reprogramming changes for immunotherapy-related cardiotoxicity is still not well understood.</p><p><strong>Methods: </strong>The CD45⁺ single-cell RNA sequencing (scRNA-seq) of the Pdcd1^-/-Ctla4^+/- and wild-type mouse heart in GSE213486 was downloaded to demonstrate the heterogeneity of immunocyte atlas in immunotherapy-related myocarditis. The liquid chromatography-tandem mass spectrometry (LC-MS/MS) spectrum metabolomics analysis detects the metabolic network differences. The drug prediction, organelle level interaction, mitochondrial level regulatory network, and phosphorylation site prediction for key regulators have also been screened via multibioinformatics analysis methods.</p><p><strong>Results: </strong>The scRNA analysis shows that the T cell is the main regulatory cell subpopulation in the pathological progress of immunotherapy-related myocarditis. Mitochondrial regulation pathway significantly participated in pseudotime trajectory- (PTT-) related differential expressed genes (DEGs) in the T cell subpopulation. Additionally, both the gene set enrichment analysis (GSEA) of PTT-related DEGs and LC-MS/MS metabolomics analysis showed that mitochondrial-regulated glycerolipid metabolism plays a central role in metabolic reprogramming changes for immunotherapy-related cardiotoxicity. Finally, the hub-regulated protease of diacylglycerol kinase zeta (Dgkz) was significantly identified and widely played various roles in glycerolipid metabolism, oxidative phosphorylation, and lipid kinase activation.</p><p><strong>Conclusion: </strong>Mitochondrial-regulated glycerolipid metabolism, especially the DGKZ protein, plays a key role in the metabolic reprogramming of immunotherapy-related myocarditis.</p>","PeriodicalId":9582,"journal":{"name":"Cardiovascular Therapeutics","volume":"2023 ","pages":"8774971"},"PeriodicalIF":3.1,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10307211/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10114979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DT-010 Exerts Cardioprotective Effects by Regulating the Crosstalk between the AMPK/PGC-1<i>α</i> Pathway and ERp57.","authors":"Xiaojing Zhang,&nbsp;Ximin Wu,&nbsp;Huihui Hu,&nbsp;Xiaoping Liu,&nbsp;Zhanfang Kang,&nbsp;Xin Deng","doi":"10.1155/2023/8047752","DOIUrl":"https://doi.org/10.1155/2023/8047752","url":null,"abstract":"<p><p>The AMP-activated protein kinase (AMPK)/peroxisome proliferator-activated receptor <i>γ</i> coactivator 1<i>α</i> (PGC-1<i>α</i>) pathway performs a crucial role in energy metabolism and mitochondrial network. Our previous study found that DT-010, a novel danshensu (DSS) and tetramethylpyrazine (TMP) conjugate, had significant cardioprotective properties <i>in vitro</i> and <i>in vivo</i>. We also reported that ERp57 served as a major target of DSS using the chemical proteomics approach. In this article, we focus on exploring the interrelationship between the regulation of the AMPK/PGC-1<i>α</i> pathway and promoting ERp57 expression induced by DT-010 in <i>tert</i>-butylhydroperoxide- (t-BHP-) induced H9c2 cell injury. The results showed that DT-010 activated the AMPK/PGC-1<i>α</i> pathway and increased ERp57 protein expression. Importantly, the above phenomenon as well as the mitochondrial function can be partially reversed by siRNA-mediated ERp57 suppression. Meanwhile, silencing AMPK significantly inhibited the ERp57 expression induced by DT-010. In addition, molecular docking and kinase assay <i>in vitro</i> revealed that DT-010 had no direct regulation effects on AMPK activity. Taken together, DT-010 exerted cardioprotective effects by regulating the crosstalk of AMPK/PGC-1<i>α</i> pathway and ERp57, representing a potential therapeutic agent for ischemic heart disease.</p>","PeriodicalId":9582,"journal":{"name":"Cardiovascular Therapeutics","volume":"2023 ","pages":"8047752"},"PeriodicalIF":3.1,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9937773/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10797191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}