Cardiovascular Therapeutics最新文献

{"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":"10.1155/2023/3939360","url":null,"abstract":"<div>\u0000 <p><i>Purpose</i>. 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. <i>Methods</i>. 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. <i>Results</i>. 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. <i>Conclusions</i>. 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>\u0000 </div>","PeriodicalId":9582,"journal":{"name":"Cardiovascular Therapeutics","volume":"2023 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2023-03-30","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":"Mass Cytometry Reveals the Imbalanced Immune State in the Peripheral Blood of Patients with Essential Hypertension","authors":"Rui Yang,&nbsp;Yuhong He,&nbsp;Honggang Zhang,&nbsp;Qiuju Zhang,&nbsp;Bingwei Li,&nbsp;Changming Xiong,&nbsp;Yubao Zou,&nbsp;Bingyang Liu","doi":"10.1155/2023/9915178","DOIUrl":"10.1155/2023/9915178","url":null,"abstract":"<div>\u0000 <p>Mounting evidence has confirmed that essential hypertension (EH) is closely related to low-grade inflammation, but there is still a lack of in-depth understanding of the state of immune cells in the circulating blood of patients with EH. We analyzed whether hypertensive peripheral blood immune cell balance was destroyed. The peripheral blood mononuclear cells (PBMCs) of all subjects were analyzed using time-of-flight cytometry (CyTOF) based on 42 kinds of metal-binding antibodies. CD45⁺ cells were categorized into 32 kinds of subsets. Compared with the health control (HC) group, the percentage of total dendritic cells, two kinds of myeloid dendritic cell subsets, one intermediate/nonclassical monocyte subset and one CD4⁺ central memory T cell subset in the EH group, was significantly higher; the percentage of low-density neutrophils, four kinds of classical monocyte subsets, one CD14^lowCD16^- monocyte subset, one naive CD4⁺ and one naive CD8⁺ T cell subsets, one CD4⁺ effector and one CD4⁺ central memory T cell subsets, one CD8⁺ effector memory T cell subset, and one terminally differentiated <i>γδ</i> T cell subset, decreased significantly in EH. What is more, the expression of many important antigens was enhanced in CD45⁺ immune cells, granulocytes, and B cells in patients with EH. In conclusion, the altered number and antigen expression of immune cells reflect the imbalanced immune state of the peripheral blood in patients with EH.</p>\u0000 </div>","PeriodicalId":9582,"journal":{"name":"Cardiovascular Therapeutics","volume":"2023 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2023-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9988372/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9082901","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-erbα Attenuates Doxorubicin-Induced Cardiotoxicity by PGC-1α Signaling Pathway","authors":"Runmei Zou,&nbsp;Shuo Wang,&nbsp;Hong Cai,&nbsp;Yuwen Wang,&nbsp;Cheng Wang","doi":"10.1155/2023/2108584","DOIUrl":"10.1155/2023/2108584","url":null,"abstract":"<div>\u0000 <p><i>Background</i>. 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. <i>Methods</i>. 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. <i>Results</i>. 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. <i>Conclusion</i>. 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>\u0000 </div>","PeriodicalId":9582,"journal":{"name":"Cardiovascular Therapeutics","volume":"2023 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2023-02-22","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":"Bardoxolone Methyl Ameliorates Myocardial Ischemia/Reperfusion Injury by Activating the Nrf2/HO-1 Signaling Pathway","authors":"Anwu Huang,&nbsp;Zhaolin Wang,&nbsp;Hua Tang,&nbsp;Zhuyin Jia,&nbsp;Xiaojun Ji,&nbsp;Xuehua Yang,&nbsp;Wenbing Jiang","doi":"10.1155/2023/5693732","DOIUrl":"10.1155/2023/5693732","url":null,"abstract":"<div>\u0000 <p><i>Background</i>. 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. <i>Methods</i>. 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&amp;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. <i>Results</i>. 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. <i>Conclusion</i>. BARD ameliorates myocardial I/R injury by inhibiting oxidative stress and cardiomyocyte apoptosis via activating the Nrf2/HO-1 pathway.</p>\u0000 </div>","PeriodicalId":9582,"journal":{"name":"Cardiovascular Therapeutics","volume":"2023 1","pages":""},"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":"DT-010 Exerts Cardioprotective Effects by Regulating the Crosstalk between the AMPK/PGC-1α 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":"10.1155/2023/8047752","url":null,"abstract":"<div>\u0000 <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>\u0000 </div>","PeriodicalId":9582,"journal":{"name":"Cardiovascular Therapeutics","volume":"2023 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2023-02-10","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}

{"title":"Identification of Potential Biomarkers for Coronary Artery Disease Based on Cuproptosis","authors":"Bohong Zhang,&nbsp;Mingliang He","doi":"10.1155/2023/5996144","DOIUrl":"10.1155/2023/5996144","url":null,"abstract":"<div>\u0000 <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>\u0000 </div>","PeriodicalId":9582,"journal":{"name":"Cardiovascular Therapeutics","volume":"2023 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2023-01-25","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":"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":"10.1155/2023/5126825","url":null,"abstract":"<div>\u0000 <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>\u0000 </div>","PeriodicalId":9582,"journal":{"name":"Cardiovascular Therapeutics","volume":"2023 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2023-01-14","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":"Social App to Improve Warfarin Therapy in Post-MHVR Chinese Patients: A Randomized Controlled Trial","authors":"Litao Zhang,&nbsp;Sha Li,&nbsp;Zishuo Li,&nbsp;Dan Yu,&nbsp;Haiyan Wu,&nbsp;Bing Hua,&nbsp;Li Xie,&nbsp;Xia Yuan,&nbsp;Yun Li,&nbsp;Zhenlu Zhang,&nbsp;Yanli Long","doi":"10.1155/2023/2342111","DOIUrl":"10.1155/2023/2342111","url":null,"abstract":"<div>\u0000 <p><i>Background.</i> Poor anticoagulation quality was a major problem among warfarin-treated patients, which called for innovative and effective methods to improve it. <i>Objective.</i> To investigate whether social app could be used to reduce warfarin-associated adverse events among post-MHVR Chinese patients. <i>Method.</i> 735 warfarin-treated patients (aged 50.8 ± 9.6 years, 59.9% female) were enrolled and randomized to a social app care group (warfarin therapy was guided by experienced clinicians via a social app) or a routine care group (warfarin therapy was managed through traditional in-office visits) at a 1 : 1 ratio. Ending points (bleeding and thrombotic events) were recorded during an 18-month follow-up period. <i>Results.</i> A total of 718 patients were included in analysis. 57 of them suffered warfarin-associated adverse events, including 30 major bleedings and 27 thrombotic events. The time in the therapeutic range (TTR, Rosendaal method) in the social app group was 71.5%, which was significantly better than 52.6% in the routine care group (difference: 18.8%, 95% CI: 16.8-20.8). Compared with the patients from the social app group, patients under routine care experienced more bleeding (hazard ratio (HR): 2.31, 95% CI: 1.13-4.72). The social app care group had lower variation (0.55 vs. 0.70) in the international normalized ratio (INR) values and fewer incidents of extremely high INR (e.g., INR &gt; 5.0, 0.87% vs. 3.42%) than the routine care group. <i>Conclusions.</i> Social app management could significantly improve warfarin control and was associated with a reduction in bleeding risk. This trial was registered with NCT03264937.</p>\u0000 </div>","PeriodicalId":9582,"journal":{"name":"Cardiovascular Therapeutics","volume":"2023 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2023-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9867580/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10576861","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 TRIB1 Variant on Lipid Profile and Coronary Artery Disease: A Systematic Review and Meta-Analysis","authors":"Baozhu Wei,&nbsp;Yang Liu,&nbsp;Hang Li,&nbsp;Yuanyuan Peng,&nbsp;Zhi Luo","doi":"10.1155/2023/4444708","DOIUrl":"10.1155/2023/4444708","url":null,"abstract":"<div>\u0000 <p><i>Background</i>. Emerging evidence indicates tribbles homolog 1 (Trib1) protein may be involved in lipid metabolism regulation and coronary artery disease (CAD) pathogenesis. However, whether <i>TRIB1</i> gene variants affect lipid levels and CAD remains elusive, this study is aimed at clarifying the effect of <i>TRIB1</i> variants on lipid profile and CAD. <i>Methods</i>. By searching PubMed and Cochrane databases for studies published before December 18, 2022, a total of 108,831 individuals were included for the analysis. <i>Results</i>. The outcomes of the analysis on all individuals showed that the A allele carriers of rs17321515 and rs2954029 variants had higher low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC) levels than the noncarriers. Consistently, a higher CAD risk was observed in the A allele carriers. Subgroup analysis indicated that increased LDL-C, TC, and CAD risk were observed in Asian population. <i>Conclusions</i>. Variants of <i>TRIB1</i> (i.e., rs17321515 and rs2954029) may serve as causal genetic markers for dyslipidemia and CAD in Asian population.</p>\u0000 </div>","PeriodicalId":9582,"journal":{"name":"Cardiovascular Therapeutics","volume":"2023 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2023-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9842430/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10583785","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,&nbsp;Ji Hae Kim","doi":"10.1155/2023/7362551","DOIUrl":"10.1155/2023/7362551","url":null,"abstract":"<div>\u0000 <p><i>Background.</i> 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. <i>Methods.</i> 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. <i>Results.</i> 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%). <i>Conclusions.</i> 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>\u0000 </div>","PeriodicalId":9582,"journal":{"name":"Cardiovascular Therapeutics","volume":"2023 1","pages":""},"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}