Rashid Ibdah, Ahmad Alrawashdeh, Sukaina Rawashdeh, Nebras Y. Melhem, Ayman J. Hammoudeh, Mohamad I. Jarrah
{"title":"Statin Eligibility according to 2013 ACC/AHA and USPSTF Guidelines among Jordanian Patients with Acute Myocardial Infarction: The Impact of Gender","authors":"Rashid Ibdah, Ahmad Alrawashdeh, Sukaina Rawashdeh, Nebras Y. Melhem, Ayman J. Hammoudeh, Mohamad I. Jarrah","doi":"10.1155/2023/5561518","DOIUrl":"10.1155/2023/5561518","url":null,"abstract":"<div>\u0000 <p>The objectives of this study were to evaluate statin eligibility among Middle Eastern patients admitted with acute myocardial infarction (AMI) who had no prior use of statin therapy, according to 2013 ACC/AHA and 2016 USPSTF guidelines, and to compare statin eligibility between men and women. This was a retrospective multicenter observational study of all adult patients admitted to five tertiary care centers in Jordan with a first-time AMI, no prior cardiovascular disease, and no prior statin use between April 2018 and June 2019. Ten-year atherosclerotic cardiovascular disease (ASCVD) risk score was estimated based on ACC/AHA risk score. A total of 774 patients met the inclusion criteria. The mean age was 55 years (SD ± 11.3), 120 (15.5%) were women, and 688 (88.9%) had at least one risk factor of cardiovascular disease. Compared to men, women were more likely to be older; had a history of diabetes, hypertension, and hypercholesterolemia; and had higher body mass index, systolic blood pressure, total cholesterol, and high-density lipoproteins. Compared to women, men were more likely to have a higher 10-year ASCVD risk score (14.0% vs. 17.8%, <i>p</i> = 0.005), and more men had a 10-year ASCVD risk score of ≥7.5% and ≥10%. The proportion of patients eligible for statin therapy was 80.2% based on the 2013 ACC/AHA guidelines and 59.5% based on the USPSTF guidelines. A higher proportion of men were eligible for statin therapy compared to women, based on both the 2013 ACC/AHA (81.4% vs. 73.5%, <i>p</i> = 0.050) and USPSTF guidelines (62.0% vs. 45.2%, <i>p</i> = 0.001). Among Middle Easterners, over half of patients with AMI would have been eligible for statin therapy prior to admission based on the 2013 ACC/AHA and USPSTF guidelines, with the presence of gender gap. Adopting these guidelines in clinical practice might positively impact primary cardiovascular preventive strategies in this region.</p>\u0000 </div>","PeriodicalId":9582,"journal":{"name":"Cardiovascular Therapeutics","volume":"2023 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2023-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10260313/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9633105","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}
Antoine J. Ribieras, Yulexi Y. Ortiz, Yan Li, Nga T. Le, Carlos T. Huerta, Francesca A. Voza, Hongwei Shao, Roberto I. Vazquez-Padron, Zhao-Jun Liu, Omaida C. Velazquez
{"title":"E-Selectin/AAV Gene Therapy Promotes Myogenesis and Skeletal Muscle Recovery in a Mouse Hindlimb Ischemia Model","authors":"Antoine J. Ribieras, Yulexi Y. Ortiz, Yan Li, Nga T. Le, Carlos T. Huerta, Francesca A. Voza, Hongwei Shao, Roberto I. Vazquez-Padron, Zhao-Jun Liu, Omaida C. Velazquez","doi":"10.1155/2023/6679390","DOIUrl":"10.1155/2023/6679390","url":null,"abstract":"<div>\u0000 <p>The response to ischemia in peripheral artery disease (PAD) depends on compensatory neovascularization and coordination of tissue regeneration. Identifying novel mechanisms regulating these processes is critical to the development of nonsurgical treatments for PAD. E-selectin is an adhesion molecule that mediates cell recruitment during neovascularization. Therapeutic priming of ischemic limb tissues with intramuscular E-selectin gene therapy promotes angiogenesis and reduces tissue loss in a murine hindlimb gangrene model. In this study, we evaluated the effects of E-selectin gene therapy on skeletal muscle recovery, specifically focusing on exercise performance and myofiber regeneration. C57BL/6J mice were treated with intramuscular E-selectin/adeno-associated virus serotype 2/2 gene therapy (E-sel/AAV) or LacZ/AAV2/2 (LacZ/AAV) as control and then subjected to femoral artery coagulation. Recovery of hindlimb perfusion was assessed by laser Doppler perfusion imaging and muscle function by treadmill exhaustion and grip strength testing. After three postoperative weeks, hindlimb muscle was harvested for immunofluorescence analysis. At all postoperative time points, mice treated with E-sel/AAV had improved hindlimb perfusion and exercise capacity. E-sel/AAV gene therapy also increased the coexpression of MyoD and Ki-67 in skeletal muscle progenitors and the proportion of Myh7<sup>+</sup> myofibers. Altogether, our findings demonstrate that in addition to improving reperfusion, intramuscular E-sel/AAV gene therapy enhances the regeneration of ischemic skeletal muscle with a corresponding benefit on exercise performance. These results suggest a potential role for E-sel/AAV gene therapy as a nonsurgical adjunct in patients with life-limiting PAD.</p>\u0000 </div>","PeriodicalId":9582,"journal":{"name":"Cardiovascular Therapeutics","volume":"2023 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2023-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10219778/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9923750","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}
Huanhuan Wang, Dan Liu, Jidong Guo, Nuerbahati Heisha, Lei Wang, Qiang Zhang, Yihui Han, Xiping Wang, Bo Zhang, Jinqing Yuan, Lijian Gao
{"title":"Analysis of the Efficacy and Safety of Coronary Catheterization through Distal Transradial Access: A Single-Center Data","authors":"Huanhuan Wang, Dan Liu, Jidong Guo, Nuerbahati Heisha, Lei Wang, Qiang Zhang, Yihui Han, Xiping Wang, Bo Zhang, Jinqing Yuan, Lijian Gao","doi":"10.1155/2023/2560659","DOIUrl":"10.1155/2023/2560659","url":null,"abstract":"<div>\u0000 <p><i>Background and Aims</i>. The distal transradial access (dTRA) is a new puncture site for coronary catheterization. We sought to evaluate the feasibility, safety, and complication rates of using the dTRA for cardiac catheterization in Chinese patients. <i>Methods</i>. A total of 263 consecutive patients who underwent catheterization through the dTRA were enrolled. The primary endpoint of the study was the rate of conversion to another access site due to the impossibility of successful artery puncture or intubation. Secondary safety endpoints were the rates of bleeding-related complications and nerve disorders. <i>Results</i>. Among 263 patients, the puncture success rate was 96.2% (253/263). Eleven patients were successfully punctured, but the guide wire was difficult to advance. One patient had intubation failure, and the success rate of intubation was 91.6% (241/263). Two hundred thirty-three patients underwent puncture via the right dTRA, 5 patients underwent puncture via the left dTRA, and 3 patients underwent puncture via the bilateral dTRA. A total of 158 (65.6%) patients underwent coronary angiography, and 83 (34.4%) patients underwent percutaneous coronary intervention. After the procedure, only 2 (0.8%) patients had mild bleeding at the puncture site, 2 (0.8%) had a forearm hematoma, and no patient had a nerve disorder. <i>Conclusions</i>. DTRA has a low incidence of complications, making it a safe and effective technique for cardiac catheterization.</p>\u0000 </div>","PeriodicalId":9582,"journal":{"name":"Cardiovascular Therapeutics","volume":"2023 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2023-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10205404/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9583362","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}
Muryam Abdul Razzaq, Waqas Younis, Muhammad Nasir Hayat Malik, Tariq G. Alsahli, Alamgeer, Shah Jahan, Roma Ehsan, Arquimedes Gasparotto Junior, Asifa Bashir
{"title":"Pulegone Prevents Hypertension through Activation of Muscarinic Receptors and Cyclooxygenase Pathway in L-NAME-Induced Hypertensive Rats","authors":"Muryam Abdul Razzaq, Waqas Younis, Muhammad Nasir Hayat Malik, Tariq G. Alsahli, Alamgeer, Shah Jahan, Roma Ehsan, Arquimedes Gasparotto Junior, Asifa Bashir","doi":"10.1155/2023/8166840","DOIUrl":"10.1155/2023/8166840","url":null,"abstract":"<div>\u0000 <p>The current study was designed to determine pulegone’s antihypertensive and vasoprotective activity in L-NAME-induced hypertensive rats. Firstly, the hypotensive dose-response relationship of pulegone was evaluated in normotensive anesthetized rats using the invasive method. Secondly, the mechanism involved in hypotensive activity was determined in the presence of pharmacological drugs such as atropine/muscarinic receptor blocker (1 mg/kg), L-NAME/NOS inhibitor (20 mg/kg), and indomethacin/COX inhibitor (5 mg/kg) in anesthetized rats. Furthermore, studies were carried out to assess the preventive effect of pulegone in L-NAME-induced hypertensive rats. Hypertension was induced in rats by administering L-NAME (40 mg/kg) orally for 28 days. Rats were divided into six groups which were treated orally with tween 80 (placebo), captopril (10 mg/kg), and different doses of pulegone (20 mg/kg, 40 mg/kg, and 80 mg/kg). Blood pressure, urine volume, sodium, and body weight were monitored weekly. After 28 days, the effect of pulegone on lipid profile, hepatic markers, antioxidant enzymes, and nitric oxide was estimated from the serum of treated rats. Moreover, plasma mRNA expression of eNOS, ACE, ICAM1, and EDN1 was measured using real-time PCR. Results show that pulegone dose-dependently decreased blood pressure and heart rate in normotensive rats, with the highest effect at 30 mg/kg/i.v. The hypotensive effect of pulegone was reduced in the presence of atropine and indomethacin, whereas L-NAME did not change its hypotensive effect. Concurrent treatment with pulegone for four weeks in L-NAME-treated rats caused a reduction in both systolic blood pressure and heart rate, reversed the reduced levels of serum nitric oxide (NO), and ameliorated lipid profile and oxidative stress markers. Treatment with pulegone also improved the vascular response to acetylcholine. Plasma mRNA expression of eNOS was reduced, whereas ACE, ICAM1, and EDN1 levels were high in the L-NAME group, which was facilitated by pulegone treatment. To conclude, pulegone prevented L-NAME-induced hypertension by demonstrating a hypotensive effect through muscarinic receptors and cyclooxygenase pathway, indicating its use as a potential candidate in managing hypertension.</p>\u0000 </div>","PeriodicalId":9582,"journal":{"name":"Cardiovascular Therapeutics","volume":"2023 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2023-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10195173/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9514731","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}
Xueting Fan, Kai Feng, Yonghui Liu, Leixi Yang, Yizhuo Zhao, Liping Tian, Yiqun Tang, Xiaozhi Wang
{"title":"miR-135a Regulates Atrial Fibrillation by Targeting Smad3","authors":"Xueting Fan, Kai Feng, Yonghui Liu, Leixi Yang, Yizhuo Zhao, Liping Tian, Yiqun Tang, Xiaozhi Wang","doi":"10.1155/2023/8811996","DOIUrl":"10.1155/2023/8811996","url":null,"abstract":"<div>\u0000 <p><i>Background</i>. Atrial fibrillation (AF) is the most common arrhythmia in clinical. Atrial fibrosis is a hallmark feature of atrial structural remodeling in AF, which is regulated by the TGF-<i>β</i>1/Smad3 pathway. Recent studies have implicated that miRNAs are involved in the process of AF. However, the regulatory mechanisms of miRNAs remain largely unknown. This study is aimed at investigating the function and regulatory network of miR-135a in AF. <i>Methods</i>. <i>In vivo</i>, the plasma was collected from patients with AF and non-AF subjects. Adult SD rats were induced by acetylcholine (ACh) (66 <i>μ</i>g/ml)-CaCl<sub>2</sub> (10 mg/ml) to establish an AF rat model. <i>In vitro</i>, atrial fibroblasts (AFs), isolated from adult SD rats, were treated with high-frequency electrical stimulation (HES) (12 h) and hypoxia (24 h) to mimic the AF and atrial fibrosis, respectively. miR-135a expression was detected through quantitative real-time polymerase chain reaction (qRT-PCR). The association between miR-135a and Smad3 was speculated by the TargetScan database and confirmed by the luciferase reporter assay. Fibrosis-related genes, Smad3, and TRPM7 were all assessed. <i>Results</i>. The expression of miR-135a was markedly decreased in the plasma of AF patients and AF rats, which was consistent with that in HES-treated and hypoxia-treated AFs. Smad3 was identified as a target of miR-135a. the downregulation of miR-135a was associated with the enhancement of Smad3/TRPM7 expressions in AFs. Additionally, the knockdown of Smad3 significantly reduced the expression of TRPM7 and further inhibited atrial fibrosis. <i>Conclusions</i>. Our study demonstrates that miR-135a regulates AF via Smad3/TRPM7, which is a potential therapeutic target for AF.</p>\u0000 </div>","PeriodicalId":9582,"journal":{"name":"Cardiovascular Therapeutics","volume":"2023 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2023-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10181910/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9869954","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}
Tian-Jun Zhao, Duan Luo, Xi Jiang, Feng Tang, Hui Jiang
{"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, Duan Luo, Xi Jiang, Feng Tang, Hui Jiang","doi":"10.1155/2023/8807278","DOIUrl":"10.1155/2023/8807278","url":null,"abstract":"<div>\u0000 <p><i>Background</i>. 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. <i>Methods</i>. 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. <i>Results</i>. 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. <i>Conclusions</i>. 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>\u0000 </div>","PeriodicalId":9582,"journal":{"name":"Cardiovascular Therapeutics","volume":"2023 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2023-04-27","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":"Cardioprotection of mAb2G4/ODN/lip on Myocardial Ischemia-Reperfusion Injury via Inhibiting the NF-κB Signaling Pathway","authors":"Zujin Xu, Zhuoran Wei, Yali Zhu, Guoqing Jing, Liufang Chen, Jia Zhan, Yun Wu","doi":"10.1155/2023/5034683","DOIUrl":"10.1155/2023/5034683","url":null,"abstract":"<div>\u0000 <p>Substantial evidence suggests that the interventions of NF-<i>κ</i>B would likely effectively prevent inflammatory response and reduce myocardial damage in the ischemic myocardium. And the NF-кB decoy ODN is a specific inhibitor that suppresses the expression of NF-<i>κ</i>B. Herein, we revealed the effect and possible mechanism of mAb2G4/ODN/lip on myocardial ischemia-reperfusion injury (MI/RI). As shown in the results, post-treatment with mAb2G4/ODN/lip improved the impaired histological morphology in the MI/RI model and elevated cell viability in the H/R model. The mAb2G4/ODN/lip complex inhibited the NLRP3 signaling pathway and decreased the expression of LDH, IL-1<i>β</i>, TNF-<i>α</i>, IL-6, and MDA. Mechanistically, we demonstrated that post-treatment with mAb2G4/ODN/lip exerted protective effects against I/R injuries by inhibiting the NF-кB-related inflammatory response. In summary, the present study may offer a novel therapeutic strategy for treating MI/RI.</p>\u0000 </div>","PeriodicalId":9582,"journal":{"name":"Cardiovascular Therapeutics","volume":"2023 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2023-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10159742/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9457959","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":"Efficacy of Acupuncture in the Treatment of Essential Hypertension: An Overview of Systematic Reviews and Meta-Analyses","authors":"Maoxia Fan, Guohua Dai, Runmin Li, Xiaoqi Wu","doi":"10.1155/2023/2722727","DOIUrl":"10.1155/2023/2722727","url":null,"abstract":"<div>\u0000 <p><i>Background</i>. Acupuncture is widely used in the clinical treatment of essential hypertension (EH). This overview is aimed at summarizing current systematic reviews of acupuncture for EH and assessing the methodological bias and quality of evidence. <i>Methods</i>. Two researchers searched and extracted 7 databases for systematic reviews (SRs)/meta-analyses (MAs) and independently assessed the methodological quality, risk of bias, reporting quality, and quality of evidence of randomized controlled trials (RCTs) included in the SRs/MAs. Tools used included the measurement tool to assess systematic reviews 2 (AMSTAR-2), the risk of bias in systematic (ROBIS) scale, the checklist of preferred reporting items for systematic reviews and meta-analyses (PRISMA), and the grading of recommendations assessment, development, and evaluation (GRADE) system. <i>Results</i>. This overview included 14 SRs/MAs that use quantitative calculations to comprehensively assess the various effects of acupuncture in essential hypertension interventions. The methodological quality, reporting quality, risk of bias, and quality of evidence for outcome measures of SRs/MAs were all unsatisfactory. According to the results of the AMSTAR-2 assessment, all SRs/MAs were of low or very low quality. According to the results of the ROBIS evaluation, a few SRs/MAs were assessed as low risk of bias. According to the results of the PRISMA checklist assessment, SRs/MAs that were not fully reported on the checklist accounted for the majority. According to the GRADE system, 86 outcomes were assessed under different interventions in SRs/MAs, and 2 were rated as moderate-quality evidence, 23 as low-quality evidence, and 61 as very low-quality evidence. Limitations of the included SRs/MAs included the lack of necessary items, such as not being registered in the protocol, not providing a list of excluded studies, and not analyzing and addressing the risk of bias. <i>Conclusion</i>. Currently, acupuncture may be an effective and safe treatment for EH, but the quality of evidence is low, and caution should be exercised when applying this evidence in clinical practice.</p>\u0000 </div>","PeriodicalId":9582,"journal":{"name":"Cardiovascular Therapeutics","volume":"2023 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2023-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10129421/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9820297","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, Huiyu Chen, Yuntao Fu, Yajun Yao, Shanqing He, Youcheng Wang, Zhen Cao, Xuewen Wang, Mei Yang, 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, Yuhong He, Honggang Zhang, Qiuju Zhang, Bingwei Li, Changming Xiong, Yubao Zou, 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<sup>+</sup> 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<sup>+</sup> 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<sup>low</sup>CD16<sup>-</sup> monocyte subset, one naive CD4<sup>+</sup> and one naive CD8<sup>+</sup> T cell subsets, one CD4<sup>+</sup> effector and one CD4<sup>+</sup> central memory T cell subsets, one CD8<sup>+</sup> 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<sup>+</sup> 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}