Cardiovascular Therapeutics最新文献

{"title":"Comparison of Different Chronic Maintenance Antithrombotic Strategies in Patients with Coronary Artery Disease: A Systematic Review and Network Meta-Analysis","authors":"Junyan Zhang,&nbsp;Zhongxiu Chen,&nbsp;Yujia Cai,&nbsp;Chen Li,&nbsp;Yong He","doi":"10.1155/2023/5446271","DOIUrl":"10.1155/2023/5446271","url":null,"abstract":"<div>\u0000 <p><i>Background</i>. Optimal antithrombotic therapy during the chronic maintenance period in patients with coronary artery disease (CAD) is unknown. We compared five kinds of mainstream chronic maintenance antithrombotic strategies at least one year after the acute phase: aspirin alone, clopidogrel alone, ticagrelor alone, continued dual antiplatelet therapy (DAPT) for a period of time, and maintenance with aspirin combined with a low-dose anticoagulant such as rivaroxaban. <i>Methods</i>. Ten randomized, controlled trials were selected using PubMed, Ovid MEDLINE, Embase, and Cochrane library through February 2023. The primary outcome was main adverse cardiac events (MACEs), and secondary outcomes include net adverse clinical events (NACEs), cardiac death, all-cause death, ischemic stroke, stent thrombosis, total bleeding, and major bleeding. A network meta-analysis was conducted with a random-effects model. Data extraction was performed by three independent reviewers. <i>Results</i>. Our search identified ten eligible randomized controlled trials enrolling a total of 82,084 patients comparing different chronic maintenance antithrombotic strategies. As for the primary endpoint, there was no statistical difference in MACE outcomes between any two of the five methods. As for the secondary endpoint, there was no statistical difference in NACE, major bleeding, all-cause death, cardiac death, and stent thrombosis between any two methods. The aspirin plus low-dose rivaroxaban group had a lower incidence of ischemic stroke compared to the aspirin group (OR = 0.49, 95% CrI 0.26-0.91). And the prolonged DAPT group had a higher total bleeding rate compared to aspirin group (OR = 2.4, 95% CrI 1.1-5.9). <i>Conclusions</i>. In terms of MACE, NACE, all-cause death, cardiac death, stent thrombosis, and major bleeding, there were no significant differences between using aspirin alone, clopidogrel alone, and ticagrelor alone; extending DAPT duration; and using aspirin combined with low-dose rivaroxaban for chronic maintenance antithrombotic regimens. However, choosing aspirin combined with low-dose rivaroxaban can reduce the incidence of ischemic stroke, and prolonged DAPT may have a higher rate of total bleeding. However, it is important to note that this study is based on indirect comparisons, and there is currently a lack of direct evidence comparing various maintenance antiplatelet therapy regimens. Further high-quality studies are needed to address this gap and provide more conclusive evidence on the comparative effectiveness of different maintenance antiplatelet strategies.</p>\u0000 </div>","PeriodicalId":9582,"journal":{"name":"Cardiovascular Therapeutics","volume":"2023 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2023-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10449594/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10464596","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":"Drug-Coated Balloon-Only Strategy for De Novo Coronary Artery Disease: A Meta-analysis of Randomized Clinical Trials","authors":"Wenyi Zhang,&nbsp;Mingduo Zhang,&nbsp;Jinfan Tian,&nbsp;Min Zhang,&nbsp;Yuan Zhou,&nbsp;Xiantao Song","doi":"10.1155/2023/3121601","DOIUrl":"10.1155/2023/3121601","url":null,"abstract":"<div>\u0000 <p><i>Backgrounds</i>. Many clinical trials have demonstrated the value of drug-coated balloons (DCB) for in-stent restenosis. However, their role in de novo lesions is not well documented. The aim of this study is to evaluate the safety and efficacy of the DCB-only strategy compared to other percutaneous coronary intervention strategies for de novo coronary lesions. <i>Methods</i>. The PubMed, Embase, Web of Science, and Cochrane Library Central Register of Controlled Trials (CENTRAL) electronic databases were searched for randomized controlled trials published up to May 6, 2023. The primary outcomes were major adverse cardiac events and late lumen loss. <i>Results</i>. A total of eighteen trials with 3336 participants were included. Compared with drug-eluting stents, the DCB-only strategy was associated with a similar risk of major adverse cardiac events (risk ratio (RR) = 0.90; 95% confidence interval (CI): 0.59 to 1.37, <i>P</i> = 0.631) and a significant decrease in late lumen loss (standardized mean difference (SMD) = −0.29, 95% CI: −0.53 to −0.04, <i>P</i> = 0.021). This effect was consistent in subgroup analysis regardless of indication, follow-up time, drug-eluting stent type, and dual antiplatelet therapy duration. However, DCBs were inferior to DESs for minimum lumen diameter and percentage diameter stenosis. The DCB-only strategy showed significantly better outcomes for most endpoints compared to plain-old balloon angioplasty or bare metal stents. <i>Conclusions</i>. Interventions with a DCB-only strategy are comparable to those of drug-eluting stents and superior to plain-old balloon angioplasty or bare metal stents for the treatment of selected de novo coronary lesions. Additional evidence is still warranted to confirm the value of DCB before widespread clinical utilization can be recommended.</p>\u0000 </div>","PeriodicalId":9582,"journal":{"name":"Cardiovascular Therapeutics","volume":"2023 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2023-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10427238/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10016536","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":"Heart Failure with Preserved Left Ventricular Ejection Fraction: A Complex Conundrum Simply Not Limited to Diastolic Dysfunction","authors":"Angel Lopez-Candales,&nbsp;Talal Asif,&nbsp;Khalid Sawalha,&nbsp;Nicholas B. Norgard","doi":"10.1155/2023/1552826","DOIUrl":"10.1155/2023/1552826","url":null,"abstract":"<div>\u0000 <p>Over the last two decades, the changing paradigm of heart failure with preserved ejection fraction (HFpEF) has transformed our understanding not only of the pathophysiology of this clinical entity but also the diagnostic and therapeutic approaches aimed at treating this complex patient population. No longer HFpEF should be seen as simply left ventricular diastolic dysfunction but as a group of that in addition of having small and thick left ventricles with abnormal diastolic filling patterns as their main pathophysiologic abnormality; they also have whole host of different abnormalities. In fact, this heterogeneous clinical entity embodies numerous mechanisms and is linked to multiorgan dysfunction, with hypertension and obesity playing a major role. Although we have gained an enormous amount of understanding not only on the causes but also the downstream effects of HFpEF, there is still much to be learned before we can fully comprehend this complex clinical entity. It is the main intention of this review to synthesize the most recent attributes, mechanism, diagnostic tools, and most useful therapeutic alternatives to be considered when evaluating patients either complaining of dyspnea on exertion as well as exercise intolerance or those recently admitted with HF symptoms but with normal LVEF in the absence of any other valvular abnormalities</p>\u0000 </div>","PeriodicalId":9582,"journal":{"name":"Cardiovascular Therapeutics","volume":"2023 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2023-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10368509/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9879702","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":"Water-Based Exercises on Peak Oxygen Consumption, Exercise Time, and Muscle Strength in Patients with Coronary Artery Disease: A Systematic Review with Meta-Analysis","authors":"Alana Lalucha Andrade Guimarães,&nbsp;Mansueto Gomes-Neto,&nbsp;Lino Sérgio Rocha Conceição,&nbsp;Micheli Bernardone Saquetto,&nbsp;Caroline Oliveira Gois,&nbsp;Vitor Oliveira Carvalho","doi":"10.1155/2023/4305474","DOIUrl":"10.1155/2023/4305474","url":null,"abstract":"<div>\u0000 <p><i>Background</i>. There is a growing use of water-based exercises in cardiac rehabilitation programs. However, there is little data concerning the effects of water-based exercise on the exercise capacity of coronary artery disease (CAD) patients. <i>Objective</i>. To perform a systematic review to investigate the effects of water-based exercise on peak oxygen consumption, exercise time, and muscle strength in patients with CAD. <i>Methods</i>. Five databases were searched to find randomized controlled trials that evaluated the effects of water-based exercise for coronary artery disease patients. Mean differences (MD) and 95% confidence intervals (CIs) were calculated, and heterogeneity was assessed using the <i>I</i>² test. <i>Results</i>. Eight studies were included. Water-based exercise resulted in an improvement in peak VO₂ of 3.4 mL/kg/min (95% CI, 2.3 to 4.5; <i>I</i>² = 0%; 5 studies, <i>N</i> = 167), exercise time of 0.6 (95% CI, 0.1 to 1.1; <i>I</i>² = 0%; 3 studies, <i>N</i> = 69), and total body strength of 32.2 kg (95% CI, 23.9 to 40.7; <i>I</i>² = 3%; 3 studies, <i>N</i> = 69) when compared to no exercising controls. Water-based exercise resulted in an improvement in peak VO₂ of 3.1 mL/kg/min (95% CI, 1.4 to 4.7; <i>I</i>² = 13%; 2 studies, <i>N</i> = 74), when compared to the plus land exercise group. No significant difference in peak VO₂ was found for participants in the water-based exercise plus land exercise group compared with the land exercise group. <i>Conclusions</i>. Water-based exercise may improve exercise capacity and should be considered as an alternative method in the rehabilitation of patients with CAD.</p>\u0000 </div>","PeriodicalId":9582,"journal":{"name":"Cardiovascular Therapeutics","volume":"2023 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2023-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10317579/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9857796","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":"10.1155/2023/8774971","url":null,"abstract":"<div>\u0000 <p><i>Background</i>. 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. <i>Methods</i>. 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. <i>Results</i>. 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. <i>Conclusion</i>. Mitochondrial-regulated glycerolipid metabolism, especially the DGKZ protein, plays a key role in the metabolic reprogramming of immunotherapy-related myocarditis.</p>\u0000 </div>","PeriodicalId":9582,"journal":{"name":"Cardiovascular Therapeutics","volume":"2023 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2023-06-21","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":"Statin Eligibility according to 2013 ACC/AHA and USPSTF Guidelines among Jordanian Patients with Acute Myocardial Infarction: The Impact of Gender","authors":"Rashid Ibdah,&nbsp;Ahmad Alrawashdeh,&nbsp;Sukaina Rawashdeh,&nbsp;Nebras Y. Melhem,&nbsp;Ayman J. Hammoudeh,&nbsp;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}

{"title":"E-Selectin/AAV Gene Therapy Promotes Myogenesis and Skeletal Muscle Recovery in a Mouse Hindlimb Ischemia Model","authors":"Antoine J. Ribieras,&nbsp;Yulexi Y. Ortiz,&nbsp;Yan Li,&nbsp;Nga T. Le,&nbsp;Carlos T. Huerta,&nbsp;Francesca A. Voza,&nbsp;Hongwei Shao,&nbsp;Roberto I. Vazquez-Padron,&nbsp;Zhao-Jun Liu,&nbsp;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⁺ 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}

{"title":"Analysis of the Efficacy and Safety of Coronary Catheterization through Distal Transradial Access: A Single-Center Data","authors":"Huanhuan Wang,&nbsp;Dan Liu,&nbsp;Jidong Guo,&nbsp;Nuerbahati Heisha,&nbsp;Lei Wang,&nbsp;Qiang Zhang,&nbsp;Yihui Han,&nbsp;Xiping Wang,&nbsp;Bo Zhang,&nbsp;Jinqing Yuan,&nbsp;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}

{"title":"Pulegone Prevents Hypertension through Activation of Muscarinic Receptors and Cyclooxygenase Pathway in L-NAME-Induced Hypertensive Rats","authors":"Muryam Abdul Razzaq,&nbsp;Waqas Younis,&nbsp;Muhammad Nasir Hayat Malik,&nbsp;Tariq G. Alsahli,&nbsp; Alamgeer,&nbsp;Shah Jahan,&nbsp;Roma Ehsan,&nbsp;Arquimedes Gasparotto Junior,&nbsp;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}

{"title":"miR-135a Regulates Atrial Fibrillation by Targeting Smad3","authors":"Xueting Fan,&nbsp;Kai Feng,&nbsp;Yonghui Liu,&nbsp;Leixi Yang,&nbsp;Yizhuo Zhao,&nbsp;Liping Tian,&nbsp;Yiqun Tang,&nbsp;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)-CaCl₂ (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}