Journal of Cardiovascular Pharmacology最新文献

{"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":"<p><strong>Abstract: </strong>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.</p>","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}

{"title":"Finerenone Proves Beneficial for Heart Failure with Preserved Ejection Fraction.","authors":"Giuseppe Biondi-Zoccai, Mattia Galli, George W Booz","doi":"10.1097/FJC.0000000000001636","DOIUrl":"10.1097/FJC.0000000000001636","url":null,"abstract":"","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142347302","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}

{"title":"Effect of an Enteral Formula Enriched with ω-3 Fatty Acids, Carnitine, and Vitamin D on Body Weight, Heart Weight, and Blood Biochemical Parameters in a Dahl Rat Heart Failure Model.","authors":"Yoshikazu Ryuno, Jun-Ichi Kobayashi, Yudai Fujimoto, Taishi Dotare, Yuya Matsue, Yoshihito Iwanami","doi":"10.1097/FJC.0000000000001637","DOIUrl":"https://doi.org/10.1097/FJC.0000000000001637","url":null,"abstract":"<p><p>Malnutrition is known to worsen the prognosis of chronic heart failure. To gain information that may be helpful in establishing appropriate nutritional interventions for chronic heart failure, the present study was performed to investigate the efficacy of nutritional management with two enteral formulas, EH, with a standard nutritional composition, and ER, fortified with omega-3 fatty acids, vitamin D, and carnitine. Experiments were performed in a Dahl rat heart failure model. After being fed a standard rodent feed (MF) containing 8% NaCl (high salt-MF [HS-MF]) from 6 to 11 weeks of age, rats were assigned to freeze-dried EH or ER diets with an NaCl concentration of 8% (HS-ER or HS-EH) until 18 weeks of age. Serum albumin was significantly higher at 14 and 17 weeks of age in rats fed the HS-ER and HS-EH diets compared with those remaining on the HS-MF diet. Body weight was also significantly higher at 14 and 17 weeks of age in animals fed the HS-ER diet, showing that nutritional deterioration was prevented. Additionally, heart weight was significantly lower at 18 weeks of age in the HS-ER group than that in the HS-MF group, suggesting that cardiac hypertrophy was prevented. This study demonstrated improved nutritional status in a heart failure model in Dahl rats presumably owing to differences in nutritional composition in the diets. Future studies are needed to explore optimal nutritional management with enteral formulas in patients with chronic heart failure.</p>","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142347301","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}

{"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}

{"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}

{"title":"Atrial hiPSC-CM as a pharmacological model to evaluate anti-AF drugs: Some lessons from IKur.","authors":"Carl Schulz,Thomas Eschenhagen,Torsten Christ","doi":"10.1097/fjc.0000000000001631","DOIUrl":"https://doi.org/10.1097/fjc.0000000000001631","url":null,"abstract":"Human induced pluripotent stem cells (hiPSC) and atrial hiPSC-derived cardiomyocytes (hiPSC-CM) have entered the arena of preclinical AF research. A central question is whether they reproduce the physiological contribution of atrial selective potassium currents (such as the ultrarapid potassium current, IKur) to repolarization. Of note, two studies in single atrial hiPSC-CM reported prolongation of action potential duration by IKur block indicating that IKur might in fact represent a valuable target for the treatment of human AF. However, the results and interpretation are at odds with the literature on IKur block in human atria and the results of clinical studies. We believe that the discrepancies indicate that experiments in single atrial CM (both adult atrial CM and atrial hiPSC-CM) might be misleading. Under particular experimental conditions, atrial hiPSC-CMs may not closely resemble the electrophysiology of the human atrium. Therefore, we recapitulate here methodological issues evaluating potential value of the IKur as an antiarrhythmic target when investigated in animal models, in human atrial tissues and finally in atrial hiPSC-CM.","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":"43 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142252439","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}

{"title":"Rethinking beta-blockers after ST-elevation myocardial infarction: essential for some, questionable for others.","authors":"Federico Russo,Angela Palma,Stefano Cacciatore,Elisa Tomarelli,Luigi Spadafora","doi":"10.1097/fjc.0000000000001632","DOIUrl":"https://doi.org/10.1097/fjc.0000000000001632","url":null,"abstract":"","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":"5 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142210436","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}

{"title":"Bivalirudin in Extracorporeal Membrane Oxygenation.","authors":"Sabrina Dunham, Patrick M Wieruszewski, James E Gerrald","doi":"10.1097/FJC.0000000000001633","DOIUrl":"https://doi.org/10.1097/FJC.0000000000001633","url":null,"abstract":"<p><strong>Abstract: </strong>Extracorporeal membrane oxygenation (ECMO) is a mechanical support treatment modality utilized in patients with refractory cardiac and/or pulmonary failure. Bleeding and thrombotic complications associated with ECMO are inherent concerns that require careful management. Anticoagulation optimization may help mitigate these risks by providing more adequate therapeutic anticoagulation and lessen the bleed risk. Heparin, the most utilized anticoagulant, carries concerns for heparin-induced thrombocytopenia and possible resistance given its dependence on co-factors and circulating proteins to exert its pharmacologic effect. In contrast, bivalirudin, a direct thrombin inhibitor, exerts its effect independent of co-factors or plasma proteins, and possesses thrombin-binding and metabolism features that may confer advantages in ECMO management. This review of the evidence for bivalirudin utilization in ECMO suggests favorable outcomes in circuit-related thrombosis, bleeding, and dosing reliability. Additionally, blood product utilization, circuit interventions, and success in ECMO decannulation and survival were positive findings associated with bivalirudin that merit consideration. Common questions and concerns relative to bivalirudin utilization, including laboratory monitoring, utilization in low flow states, dosing considerations in renal replacement therapy, reversibility, and cost are also discussed in this review. Moreover, this review suggests that bivalirudin utilization presents the opportunity for ECMO management simplification.</p>","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142288004","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}

{"title":"Anthocyanins in Vascular Health and Disease: Mechanisms of Action and Therapeutic Potential.","authors":"Yaping Zhao, Li Wang, Yu Huang, Paul C Evans, Peter J Little, Xiaoyu Tian, Jianping Weng, Suowen Xu","doi":"10.1097/FJC.0000000000001602","DOIUrl":"https://doi.org/10.1097/FJC.0000000000001602","url":null,"abstract":"<p><strong>Abstract: </strong>Unhealthy lifestyles have placed a significant burden on individuals' cardiovascular health. Anthocyanins are water-soluble flavonoid pigments found in a wide array of common foods and fruits. Anthocyanins have the potential to contribute to the prevention and treatment of cardiovascular disease by improving lipid profiles and vascular function, reducing blood glucose levels and blood pressure, and inhibiting inflammation. These actions have been demonstrated in numerous clinical and preclinical studies. At the cellular and molecular level, anthocyanins and their metabolites could protect endothelial cells from senescence, apoptosis, and inflammation by activating the phosphoinositide 3-kinase/protein kinase B/endothelial nitric oxide synthases, silent information regulator 1 (SIRT1), or nuclear factor erythroid2-related factor 2 pathways and inhibiting the nuclear factor kappa B, Bax, or P38 mitogen-activated protein kinase pathways. Furthermore, anthocyanins prevent vascular smooth muscle cell from platelet-derived growth factor -induced or tumor necrosis factor-α-induced proliferation and migration by inhibiting the focal adhesion kinase and extracellular regulated protein kinases signaling pathways. Anthocyanins could also attenuate vascular inflammation by reducing the formation of oxidized lipids, preventing leukocyte adhesion and infiltration of the vessel wall, and macrophage phagocytosis of deposited lipids through reducing the expression of cluster of differentiation 36 and increasing the expression of ATP-binding cassette subfamily A member 1 and ATP-binding cassette subfamily G member 1. At the same time, anthocyanins could lower the risk of thrombosis by inhibiting platelet activation and aggregation through down-regulating P-selectin, transforming growth factor-1, and CD40L. Thus, the development of anthocyanin-based supplements or derivative drugs could provide new therapeutic approaches to the prevention and treatment of vascular diseases.</p>","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":"84 3","pages":"289-302"},"PeriodicalIF":2.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142143075","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}

{"title":"Fondaparinux Sodium for Anticoagulant Therapy After Primary Percutaneous Coronary Intervention: A Single-Center Randomized Trial in China.","authors":"Yi-Yi Li, Xin-Jing Zhong, Jun-Ting Luo, Chun-Mei Zeng, He Li, Li-Qiu Zhong, Guang-Xin Zou","doi":"10.1097/FJC.0000000000001596","DOIUrl":"https://doi.org/10.1097/FJC.0000000000001596","url":null,"abstract":"<p><strong>Abstract: </strong>In this study, we investigated the safety and efficacy of fondaparinux sodium in postpercutaneous coronary intervention (PCI) anticoagulation therapy for patients with ST-segment elevation myocardial infarction. There are a total of 200 patients with ST segment elevation myocardial infarction underwent PCI and anticoagulation therapy. They were randomly split into experimental (n = 108) and control groups (n = 92). The experimental group received postoperative fondaparinux sodium (2.5 mg q.d), while the control group received enoxaparin (4000 IU q12 h). We did not use a loading dose for enoxaparin. Bleeding incidence and major adverse cardiovascular/cerebrovascular events were monitored during hospitalization, and at 1, 3, and 6 months postsurgery. The primary end points, including bleeding, mortality, and myocardial infarction during hospitalization, were not significantly different between the 2 groups. For secondary end points, the incidence of combined end point events at 1 month, 3 months, and 6 months after surgery in the experimental group was lower than in the control group (P < 0.05). According to Cox regression analysis, the risk of bleeding in the experimental group was significantly lower than that in the control group [hazard ratios: 0.506, 95% confidence interval (CI): 0.284-0.900] (P = 0.020). The risk of mortality in the experimental group was significantly lower than in the control group (hazard ratio: 0.188, 95% CI: 0.040-0.889) (P = 0.035). In summary, perioperative use of fondaparinux sodium during PCI in patients with STEMI in this study was associated with a lower risk of bleeding and death compared with enoxaparin use in the absence of loading dose.</p>","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":"84 3","pages":"331-339"},"PeriodicalIF":2.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142143076","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}