Journal of Cardiovascular Pharmacology最新文献_第8页

The Efficacy of I Na Block to Cardiovert Atrial Fibrillation Is Enhanced by Inhibition of I K1. 抑制 IK1 可增强 INa 阻滞对心房颤动的心脏复律疗效。

IF 2.6 4区医学

Journal of Cardiovascular Pharmacology Pub Date : 2024-10-01 DOI: 10.1097/FJC.0000000000001617

Alexander Burashnikov, Charles Antzelevitch

{"title":"The Efficacy of I Na Block to Cardiovert Atrial Fibrillation Is Enhanced by Inhibition of I K1.","authors":"Alexander Burashnikov, Charles Antzelevitch","doi":"10.1097/FJC.0000000000001617","DOIUrl":"10.1097/FJC.0000000000001617","url":null,"abstract":"Abstract: There is a need for more efficient pharmacological cardioversion of atrial fibrillation (AF). We tested the hypothesis that inhibition of I K1 significantly enhances the efficacy of I Na block to depress atrial excitability and to cardiovert AF. The study was conducted in canine isolated arterially perfused right atrial preparations with rim of ventricular tissue. AF was induced in the presence of acetylcholine (ACh; 0.5 µM). BaCl 2 (10 µM) was used to inhibit I K1 and flecainide (1.5 µM) to block I Na . Sustained AF (>45 minutes) was recorded in 100% atria (5/5) in the presence of ACh alone. Flecainide cardioverted AF in 50% of atria (4/8), BaCl 2 in 0% (0/5), and their combination in 100% (5/5). AF cardioversion occurred in 15 ± 9 minutes with flecainide alone (n = 4) and in 8 ± 9 minutes with the combination (n = 5). Following drug-induced AF cardioversion, AF was inducible in 4/4 atria with flecainide alone (≤5 minutes duration) and in 2/5 atria with the combination (≤30 seconds duration). Atrial excitability was significantly more depressed by combined versus monotherapies. There was little to no effect on ventricular excitability under any condition tested. Thus, inhibition of I K1 significantly enhances the efficacy of flecainide to depress atrial excitability and to cardiovert AF in our experimental setting. A combination of I Na and I K1 inhibition may be an effective approach for cardioversion of AF.","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":" ","pages":"434-439"},"PeriodicalIF":2.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141901868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Nrf2 Ameliorates Atrial Fibrosis During Antithrombotic Therapy for Atrial Fibrillation by Modulating CYP2C9 Activity. Nrf2通过调节CYP2C9的活性改善心房颤动抗栓治疗期间的心房纤维化。

IF 2.6 4区医学

Journal of Cardiovascular Pharmacology Pub Date : 2024-10-01 DOI: 10.1097/FJC.0000000000001618

Liting Wu, Zhumeng Li, Lijuan Xu, Yingchao Fan, Delong Mao, Hanxiao Sun, Wenfang Zhuang

{"title":"Nrf2 Ameliorates Atrial Fibrosis During Antithrombotic Therapy for Atrial Fibrillation by Modulating CYP2C9 Activity.","authors":"Liting Wu, Zhumeng Li, Lijuan Xu, Yingchao Fan, Delong Mao, Hanxiao Sun, Wenfang Zhuang","doi":"10.1097/FJC.0000000000001618","DOIUrl":"10.1097/FJC.0000000000001618","url":null,"abstract":"Abstract: Anticoagulant therapy can significantly reduce the incidence of stroke and peripheral embolism events in patients with atrial fibrillation (AF). Although warfarin is widely used as an anticoagulant drug, a wrong dose can lead to increased risks of bleeding or blood clots. The aim of this study was to assess whether nuclear factor-erythroid-2-related factor 2 (Nrf2) can improve the efficacy of warfarin through the regulation of cytochrome P450 family 2 subfamily C member 9 (CYP2C9) using a rat model of AF. Results showed that AF significantly reduced Nrf2 in myocardial tissue of sham-operated rats. Furthermore, Nrf2 overexpression effectively reduced AF-induced atrial fibrosis by reducing collagen in the left atrium, inhibiting the expression of the fibrosis-related genes collagen I and transforming growth factor-β1 in rats with AF. Nrf2 overexpression can activate CYP2C9, decrease the serum concentration of warfarin, and decrease prothrombin time and international normalized ratio in AF rats. In this article, Nrf2 overexpression protects against fibrosis, increased survival in AF rats, and activated CYP2C9 expression, thus broadening the therapeutic range of warfarin in AF rats.","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":" ","pages":"440-450"},"PeriodicalIF":2.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11446533/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141988075","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}

引用次数: 0

The Combination of Valsartan and Spironolactone Mitigated Mitral Regurgitation-Induced Cardiac Dysfunction in a Novel Rat Model. 在一种新型大鼠模型中，缬沙坦和螺内酯联用可减轻二尖瓣反流引起的心功能不全。

IF 2.6 4区医学

Journal of Cardiovascular Pharmacology Pub Date : 2024-10-01 DOI: 10.1097/FJC.0000000000001614

Wei-Ting Chang, Yu-Wen Lin, Chin-Yu Chen, Chon-Seng Hong, Zhih-Cherng Chen, You-Cheng Lin, Jhih-Yuan Shih

{"title":"The Combination of Valsartan and Spironolactone Mitigated Mitral Regurgitation-Induced Cardiac Dysfunction in a Novel Rat Model.","authors":"Wei-Ting Chang, Yu-Wen Lin, Chin-Yu Chen, Chon-Seng Hong, Zhih-Cherng Chen, You-Cheng Lin, Jhih-Yuan Shih","doi":"10.1097/FJC.0000000000001614","DOIUrl":"10.1097/FJC.0000000000001614","url":null,"abstract":"Abstract: Despite its high prevalence, effective treatment for degenerative mitral regurgitation (MR) remains elusive. Although the mineralocorticoid-receptor antagonist spironolactone, in conjunction with renin-angiotensin-aldosterone system inhibitors, has been shown to reduce mortality in patients with heart failure with reduced ejection fraction, its efficacy in managing degenerative MR is uncertain. In this study, we aimed to compare the effectiveness of valsartan (a renin-angiotensin system inhibitor), spironolactone, and combination therapy in mitigating MR-induced myocardial dysfunction. Using a mini-invasive model of degenerative MR, we administered valsartan (31 mg/kg/d), spironolactone (80 mg/kg/d), or a combination of both to rats over a 4-week period. Serial echocardiography and pressure-volume loops were utilized to assess cardiac function and hemodynamics. Rats with degenerative MR treated with valsartan or spironolactone alone did not show significant improvement in myocardial dysfunction. In contrast, combination therapy resulted in significant improvement. Similarly, the pressure-volume relationship was significantly improved in rats treated with the combination therapy compared with that in rats treated with a single therapy. Mechanistically, combination therapy effectively suppressed circulating and cardiac expression of aldosterone- and apoptosis-associated proteins. Overall, combination treatment with valsartan and spironolactone significantly attenuated the degenerative MR-induced myocardial stress and dysfunction, suggesting a potential therapeutic avenue for managing degenerative MR-induced heart failure.","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":" ","pages":"410-417"},"PeriodicalIF":2.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141901867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Metolazone Versus Chlorothiazide in Acute Heart Failure Patients With Diuretic Resistance and Renal Dysfunction: A Retrospective Cohort Study. 美托拉宗与氯噻嗪对利尿剂耐药性和肾功能不全的急性心力衰竭患者的对比：一项回顾性队列研究。

IF 2.6 4区医学

Journal of Cardiovascular Pharmacology Pub Date : 2024-10-01 DOI: 10.1097/FJC.0000000000001623

Caitlin M Gibson, Meghan M Beard, Alisa K Escano, Brittany L Good, Teresa G Potter, Albert M Truong, Benjamin Van Tassell

{"title":"Metolazone Versus Chlorothiazide in Acute Heart Failure Patients With Diuretic Resistance and Renal Dysfunction: A Retrospective Cohort Study.","authors":"Caitlin M Gibson, Meghan M Beard, Alisa K Escano, Brittany L Good, Teresa G Potter, Albert M Truong, Benjamin Van Tassell","doi":"10.1097/FJC.0000000000001623","DOIUrl":"10.1097/FJC.0000000000001623","url":null,"abstract":"Abstract: Guidelines recommend intravenous loop diuretics as first-line therapy for patients hospitalized with acute heart failure (AHF) and volume overload. Additional agents can be used for augmentation, but there is limited guidance on agent selection. The study objective was to determine if chlorothiazide or metolazone is associated with differences in diuretic efficacy or safety in loop diuretic-resistant patients with AHF and renal dysfunction (eGFR <45 mL/min/1.73 m²). We conducted a multicenter, retrospective cohort study of patients hospitalized with AHF and renal dysfunction who received metolazone or chlorothiazide in addition to intravenous loop diuretics. The primary end point was a comparison of 24-hour urine output (UOP) between the 24 hours before and after thiazide administration. Secondary and safety end points included weight change, requirement for vasopressors or inotropes, electrolyte abnormalities, and changes in renal function. A total of 221 patients were included. The mean daily diuretic doses were chlorothiazide 632 mg and metolazone 7 mg. The mean 24-hour UOP increased more among chlorothiazide-treated (from 1668 mL to 3826 mL) versus metolazone-treated patients (from 1672 mL to 2834 mL) ( P < 0.001) after the addition of the second diuretic. Statistically significant reductions in serum creatinine were observed in the chlorothiazide group following 72 hours of treatment ( P = 0.016). More hypomagnesemia was observed in the chlorothiazide group; no differences in other electrolytes or changes in weight were observed. Overall, chlorothiazide was associated with a greater increase in 24-hour UOP than metolazone without an excess of potassium or serum creatinine derangements. However, weight changes did not differ significantly between groups. Future prospective studies are needed to confirm potential differences in diuretic response and safety.","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":" ","pages":"451-456"},"PeriodicalIF":2.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141901865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Valtrate Suppresses TNFSF14-Mediated Arrhythmia After Myocardial Ischemia-Reperfusion by Inducing N-linked Glycosylation of LTβR to Regulate MGA/MAX/c-Myc/Cx43. 戊酸盐通过诱导LTβR的N-连接糖基化来调节MGA/MAX/c-Myc/Cx43，从而抑制心肌缺血再灌注后TNFSF14介导的心律失常。

IF 2.6 4区医学

Journal of Cardiovascular Pharmacology Pub Date : 2024-10-01 DOI: 10.1097/FJC.0000000000001613

Jing Zhang, Xiaoqi Xiong, Jun Li, Changjun Luo, Qiang Su, Xin Hao, Qiang Wu, Wanzhong Huang

{"title":"Valtrate Suppresses TNFSF14-Mediated Arrhythmia After Myocardial Ischemia-Reperfusion by Inducing N-linked Glycosylation of LTβR to Regulate MGA/MAX/c-Myc/Cx43.","authors":"Jing Zhang, Xiaoqi Xiong, Jun Li, Changjun Luo, Qiang Su, Xin Hao, Qiang Wu, Wanzhong Huang","doi":"10.1097/FJC.0000000000001613","DOIUrl":"10.1097/FJC.0000000000001613","url":null,"abstract":"Abstract: Myocardial ischemia-reperfusion (MIR)-induced arrhythmia remains a major cause of death in patients with cardiovascular diseases. The reduction of Cx43 has been known as a major inducer of arrhythmias after MIR, but the reason for the reduction of Cx43 remains largely unknown. The aim of this study was to find the key mechanism underlying the reduction of Cx43 after MIR and to screen out an herbal extract to attenuate arrhythmia after MIR. The differentially expressed genes in the peripheral blood mononuclear cell (PBMCs) after MIR were analyzed using the data from several gene expression omnibus data sets, followed by the identification in PBMCs and the serum of patients with myocardial infarction. Tumor necrosis factor superfamily protein 14 (TNFSF14) was increased in PBMCs and the serum of patients, which might be associated with the injury after MIR. The toxic effects of TNFSF14 on cardiomyocytes were investigated in vitro . Valtrate was screened out from several herbal extracts. Its protection against TNFSF14-induced injury was evaluated in cardiomyocytes and animal models with MIR. Recombinant TNFSF14 protein not only suppressed the viability of cardiomyocytes but also decreased Cx43 by stimulating the receptor LTβR. LTβR induces the competitive binding of MAX to MGA rather than the transcriptional factor c-Myc, thereby suppressing c-Myc-mediated transcription of Cx43. Valtrate promoted the N-linked glycosylation modification of LTβR, which reversed TNFSF14-induced reduction of Cx43 and attenuated arrhythmia after MIR. In all, valtrate suppresses TNFSF14-induced reduction of Cx43, thereby attenuating arrhythmia after MIR.","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":" ","pages":"418-433"},"PeriodicalIF":2.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141727295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Sjogren Syndrome and Outcomes of Acute Myocardial Infarction: A Propensity Score-Matched Analysis of the Nationwide Inpatient Sample 2005-2018. Sjogren综合征与急性心肌梗死的预后：2005-2018年全国住院患者样本倾向得分匹配分析》。

IF 2.6 4区医学

Journal of Cardiovascular Pharmacology Pub Date : 2024-10-01 DOI: 10.1097/FJC.0000000000001603

Bu-Yuan Hsiao

{"title":"Sjogren Syndrome and Outcomes of Acute Myocardial Infarction: A Propensity Score-Matched Analysis of the Nationwide Inpatient Sample 2005-2018.","authors":"Bu-Yuan Hsiao","doi":"10.1097/FJC.0000000000001603","DOIUrl":"10.1097/FJC.0000000000001603","url":null,"abstract":"Abstract: The aim of this study was to evaluate the potential associations between Sjogren syndrome and outcomes of acute myocardial infarction (AMI) hospitalization. This population-based, retrospective observational study extracted data from the US Nationwide Inpatient Sample between 2005 and 2018. Adults aged 20 years or older hospitalized for AMI were eligible for inclusion. Propensity score matching was applied to balance the characteristics between the comparison groups (ie, with and without Sjogren syndrome). Associations between Sjogren syndrome and in-hospital outcomes were determined using univariate and multivariable logistic regression analyses. A total of 1,735,142 patients were included. After propensity score matching, 4740 patients remained for subsequent analyses (948 had Sjogren syndrome and 3792 did not). After adjustment, patients with Sjogren syndrome had significantly lower in-hospital mortality (adjusted OR: 0.52, 95% CI, 0.36-0.73, P < 0.001), prolonged length of stay (aOR: 0.83, 95% CI, 0.69-0.995, P = 0.044), cardiogenic shock (aOR: 0.58, 95% CI, 0.40-0.83, P = 0.004), cardiac dysrhythmias (aOR: 0.77, 95% CI, 0.66-0.90, P < 0.001), acute kidney injury (aOR: 0.56, 95% CI, 0.45-0.70, P < 0.001), or respiratory failure (aOR: 0.63, 95% CI, 0.48-0.81, P < 0.001) than those without Sjogren syndrome. The stratified analysis revealed that Sjogren syndrome was associated with decreased odds of in-hospital mortality in patients with non-ST elevation myocardial infarction or ST-elevation myocardial infarction. In conclusion, among patients admitted to US hospitals for AMI, the patients with Sjogren syndrome have a lowered probability of in-hospital mortality, certain morbidities, and prolonged length of stay. Further investigations should be conducted to establish a robust understanding of the associations observed.","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":" ","pages":"394-399"},"PeriodicalIF":2.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141723715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Impact of Hydrogen Sulfide in the Paraventricular Nucleus on the MAPK Pathway in High Salt-Induced Hypertension. 室旁核中的硫化氢对高盐诱发高血压的 MAPK 通路的影响

IF 2.6 4区医学

Journal of Cardiovascular Pharmacology Pub Date : 2024-10-01 DOI: 10.1097/FJC.0000000000001622

Yan-Feng Liang, Qing-Xin You, Shu-Yue Chen, Lei Ni, Xiang-Lian Meng, Jian-Xiang Gao, Yong-Bo Ren, Han-Jun Song, Jia-Lu Su, Yang Teng, Qing-Yun Gu, Chao Lv, Bo-Yang Yuan, Xuan Wang, Yong-Tai Zheng, Dong-Dong Zhang

{"title":"The Impact of Hydrogen Sulfide in the Paraventricular Nucleus on the MAPK Pathway in High Salt-Induced Hypertension.","authors":"Yan-Feng Liang, Qing-Xin You, Shu-Yue Chen, Lei Ni, Xiang-Lian Meng, Jian-Xiang Gao, Yong-Bo Ren, Han-Jun Song, Jia-Lu Su, Yang Teng, Qing-Yun Gu, Chao Lv, Bo-Yang Yuan, Xuan Wang, Yong-Tai Zheng, Dong-Dong Zhang","doi":"10.1097/FJC.0000000000001622","DOIUrl":"10.1097/FJC.0000000000001622","url":null,"abstract":"Abstract: The hypothalamic paraventricular nucleus (PVN) plays a central role in regulating cardiovascular activity and blood pressure. We administered hydroxylamine hydrochloride (HA), a cystathionine-β-synthase inhibitor, into the PVN to suppress endogenous hydrogen sulfide and investigate its effects on the mitogen-activated protein kinase (MAPK) pathway in high salt (HS)-induced hypertension. We randomly divided 40 male Dahl salt-sensitive rats into 4 groups: the normal salt (NS) + PVN vehicle group, the NS + PVN HA group, the HS + PVN vehicle group, and the HS + PVN HA group, with 10 rats in each group. The rats in the NS groups were fed a NS diet containing 0.3% NaCl, while the HS groups were fed a HS diet containing 8% NaCl. The mean arterial pressure was calculated after noninvasive measurement using an automatic sphygmomanometer to occlude the tail cuff once a week. HA or vehicle was infused into the bilateral PVN using Alzet osmotic mini pumps for 6 weeks after the hypertension model was successfully established. We measured the levels of H 2 S in the PVN and plasma norepinephrine using enzyme linked immunosorbent assay. In addition, we assessed the parameters of the MAPK pathway, inflammation, and oxidative stress through western blotting, immunohistochemical analysis, or real-time polymerase chain reaction. In this study, we discovered that decreased levels of endogenous hydrogen sulfide in the PVN contributed to the onset of HS-induced hypertension. This was linked to the activation of the MAPK signaling pathway, proinflammatory cytokines, and oxidative stress in the PVN, as well as the activation of the sympathetic nervous system.","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":" ","pages":"468-478"},"PeriodicalIF":2.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11446517/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141901869","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}

引用次数: 0

From Risk to Resilience: Improved Outcomes After Myocardial Infarction in Patients With Sjogren's Syndrome. 从风险到恢复力：改善斯约格伦综合征患者心肌梗死后的预后。

IF 2.6 4区医学

Journal of Cardiovascular Pharmacology Pub Date : 2024-10-01 DOI: 10.1097/FJC.0000000000001615

Catherine X Wright, Attila Feher

引用次数: 0

PDE8 Inhibition and Its Impact on ICa,L in Persistent Atrial Fibrillation: Evaluation of PDE8 as a Potential Drug Target. PDE8 抑制及其对持续性心房颤动 ICa,L 的影响：评估作为潜在药物靶点的 PDE8。

IF 3 4区医学

Journal of Cardiovascular Pharmacology Pub Date : 2024-09-13 DOI: 10.1097/fjc.0000000000001630

Djemail Ismaili,Johannes Petersen,Carl Schulz,Thomas Eschenhagen,Jussi T Koivumäki,Torsten Christ

{"title":"PDE8 Inhibition and Its Impact on ICa,L in Persistent Atrial Fibrillation: Evaluation of PDE8 as a Potential Drug Target.","authors":"Djemail Ismaili,Johannes Petersen,Carl Schulz,Thomas Eschenhagen,Jussi T Koivumäki,Torsten Christ","doi":"10.1097/fjc.0000000000001630","DOIUrl":"https://doi.org/10.1097/fjc.0000000000001630","url":null,"abstract":"Atrial fibrillation (AF) poses a significant therapeutic challenge with drug interventions showing only limited success. Phosphodiesterases (PDE) regulate cardiac electrical stability and may represent an interesting target. Recently, PDE8 inhibition was proposed as an antiarrhythmic intervention by increasing L-type Ca2+ current (ICa,L) and action potential duration (APD). However, the effect size of PDE8 inhibition on ICa,L and APD seems discrepant and effects on force are unknown. We investigated the impact of PDE8 inhibition on force using PF-04957325 in right atrial appendages, obtained from patients in sinus rhythm (SR) and with persistent AF (peAF) undergoing cardiac surgery. A computational model was employed to predict the effects of PDE8 inhibition on APD in SR and peAF. Results showed no increase in force after exposure to increasing concentrations of the PDE8 inhibitor PF-04957325 in either SR or peAF tissues. Furthermore, PDE8 inhibition did not affect the potency or efficacy of norepinephrine-induced inotropic effects in either group. Arrhythmic events triggered by norepinephrine were observed in both SR and peAF, but their frequency remained unaffected by PF-04957325 treatment. Computational modeling predicted that the reported increase in ICa,L induced by PDE8 inhibition would lead to substantial APD prolongation at all repolarization states, particularly in peAF. Our findings indicate that PDE8 inhibition does not significantly impact force or arrhythmogenicity in human atrial tissue.","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":"42 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142252396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Peroxisome Proliferator-Activated Receptor Gamma Regulates Interleukin-6-Induced Lipoprotein (a) Gene Expression in Human HepG2 Cells. 过氧化物酶体增殖激活受体γ调节白细胞介素-6 诱导的人 HepG2 细胞中脂蛋白（a）基因表达。

IF 3 4区医学

Journal of Cardiovascular Pharmacology Pub Date : 2024-09-13 DOI: 10.1097/fjc.0000000000001634

Tarek Harb,Efthymios Ziogos,Núria Amat-Alarcon,Shenghan Lai,Gary Gerstenblith,Marios Arvanitis,Thorsten M Leucker

{"title":"Peroxisome Proliferator-Activated Receptor Gamma Regulates Interleukin-6-Induced Lipoprotein (a) Gene Expression in Human HepG2 Cells.","authors":"Tarek Harb,Efthymios Ziogos,Núria Amat-Alarcon,Shenghan Lai,Gary Gerstenblith,Marios Arvanitis,Thorsten M Leucker","doi":"10.1097/fjc.0000000000001634","DOIUrl":"https://doi.org/10.1097/fjc.0000000000001634","url":null,"abstract":"Lipoprotein(a) [Lp(a)] is a risk factor for coronary disease. Although levels are primarily genetically determined, data from patients with inflammatory diseases indicate that the inflammatory milieu is associated with increased Lp(a) levels. Lp(a) is synthesized in the liver and the LPA gene promoter contains an interleukin-6 (IL-6) responsive binding site, but the regulatory steps linking inflammation with hepatic Lp(a) synthesis are not well clarified. We explored the interplay between IL-6, peroxisome proliferator-activated receptor gamma (PPARγ), and Lp(a) synthesis in HepG2 cells. Through genetic mapping, a regulatory variant within the LPA promoter overlapping with a PPARγ binding site was identified. In in vitro experiments, IL-6-mediated LPA gene transcription was heightened with PPARγ knock-down and suppressed with pioglitazone, a PPARγ agonist. These results demonstrate an important role of PPARγ as a negative regulator of IL-6 induced hepatic Lp(a) production and may represent a new therapeutic target for patients with inflammatory conditions characterized by elevated Lp(a).","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":"42 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142252438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0