Journal of Cardiovascular Pharmacology最新文献

{"title":"The 5-HT7 receptor contributes to increased hindquarter blood flow caused by skeletal muscle contraction.","authors":"Teresa Krieger-Burke, Elise Yoder, Jefferson C Frisbee, Hannah Garver, Gregory D Fink, Stephanie W Watts","doi":"10.1097/FJC.0000000000001688","DOIUrl":"10.1097/FJC.0000000000001688","url":null,"abstract":"<p><p>Serotonin (5-hydroxytryptamine, 5-HT) at low plasma concentrations reduces blood pressure and dilates some skeletal muscle arterioles in the rat. We hypothesized that the 5-HT7 receptor is essential for both 5-HT-induced changes in blood pressure and skeletal muscle arteriolar function. Male 5-HT7 receptor knock out (KO) rats under isoflurane anesthesia had a higher resting hindquarter vascular resistance [HQVR; mm Hg/ml/min; KO (16.0+2.0) vs WT (10.8+0.6.0), p = 0.04]; this was not observed in females. The reduction in blood pressure and HQVR caused by intravenous infusion of 5-HT (25 μg/kg/min) was attenuated (∼56%) in male and female KO rats vs WT. Left anterior descending (LAD) coronary arterial ligation was used to create a model of impaired hindquarter perfusion and exercise intolerance. The goal was to determine whether heart failure associated skeletal muscle blood flow abnormalities were affected by loss of a functioning 5-HT7 receptor in skeletal muscle vasculature. Transdermal neuromuscular electrical stimulation (NMES) was used to mimic exercise induced contraction of skeletal muscle and increase blood flow in the hindquarters (HQ). Male (M) and female (F) 5-HT7 receptor KO rats had a profoundly reduced ability to increase HQ flow during NMES vs WT (% increase from basal; M WT = 118.0+18.0 vs KO=14.6+7.1%; F WT= 101.0+12.0 vs KO = 7.6+6.0%), observed in sham and LAD rats. In a naive cohort of 5-HT7 WT and KO rats, NMES-induced increases in HQ flow did not occur in 5-HT7 receptor KO rats. The NMES-induced increase in HQ flow was also abolished in the presence of the 5-HT7 receptor antagonist SB269970 in normal Sprague-Dawley rats. Lectin visualization of gastrocnemius muscle microvasculature indicateded that the elevated HQVR at rest in male 5-HT7 receptor KO rats was not due to a reduced microvascular density vs the WT. We conclude that 5-HT acting at least in part via the 5-HT7 receptor may have a larger role in (patho)physiological regulation of the circulation than has been heretofore appreciated.</p>","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143527788","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":"Cardiac Immunotherapy, Immuno-Cardiology and the Future of Cardiovascular Pharmacology.","authors":"Giuseppe Biondi-Zoccai, Brittany N Weber, Antonio Abbate, George W Booz","doi":"10.1097/FJC.0000000000001687","DOIUrl":"10.1097/FJC.0000000000001687","url":null,"abstract":"<p><p>Immuno-cardiology is an emerging field that explores the interplay between the immune system, inflammation and cardiovascular health/disease, aiming to develop innovative therapies for preventing and treating cardiac diseases. Indeed, chronic inflammation and immune dysregulation play pivotal roles in most cardiovascular conditions, including arrhythmias, atherothrombosis, ischemic heart disease, heart failure, and valve disease. Recent advances in immune-based therapies, including chimeric antigen receptor (CAR)-T and CAR-macrophage (CAR-M) technologies, have demonstrated potential in impacting on cardiac fibrosis and thus improving surrogate endpoints in preclinical studies. Immune checkpoint inhibitors (ICIs), while already established as an effective intervention in oncology, present challenges in their cardiovascular applications due to cardiotoxic side effects, highlighting the need for dedicated cardioprotective strategies or further molecular refinements. Nanoparticle-based delivery systems and cytokine-targeted therapies may offer precise modulation of immune responses, while gut microbiota interventions could exploit the systemic impact of inflammation on cardiovascular health. Despite these quite promising advances, barriers such as safety, scalability, and patient-specific responses must be addressed, and thus precision and personalized approaches will be crucial to overcoming these challenges and ensuring safe and also equitable access. By leveraging interdisciplinary collaboration and technological innovations, immuno-cardiology holds the promise of transforming the prevention and treatment landscape for cardiac diseases, paving the way for improved outcomes and quality of life for patients worldwide.</p>","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143523591","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":"Procyanidin B2 attenuates pathological cardiac fibrosis and inflammation: role of PPARγ.","authors":"Chun Xia Li, Ruo Man Wu, Qian Lin Xie, Fei Wang, Xiao Le Xu","doi":"10.1097/FJC.0000000000001684","DOIUrl":"https://doi.org/10.1097/FJC.0000000000001684","url":null,"abstract":"<p><p>Procyanidin B2 (PB2) is a prominent procyanidin isomer. Its effects and mechanisms in cardiac remodeling are not fully understood. Peroxisome proliferator-activated receptor gamma (PPAR-γ) plays a crucial role in regulating cardiac hypertrophy, fibrosis, and inflammation. This study aims to investigate the effect of PB2 on pathological cardiac fibrosis and inflammation, focusing on the underlying mechanisms involving PPAR-γ. In vitro, cardiac fibrosis was induced in cardiac fibroblasts using angiotensin II. In vivo, a mouse model of pathological cardiac fibrosis was generated through transverse aortic constriction to induce pressure overload. We found that PB2 inhibited proliferation, differentiation, collagen accumulation, and the NF-κB inflammation pathway in cardiac fibroblasts triggered by angiotensin II. These inhibitory effects were negated by the PPAR-γ antagonist GW9662 and RNA interference. Additionally, PB2 directly elevated PPAR-γ expression in cardiac fibroblasts. Similarly, PB2 alleviated transverse aortic constriction-induced cardiac dysfunction, myocardial fibrosis, and inflammation in mice. These cardioprotective effects of PB2 in vivo were counteracted by co-administration with GW9662. Correspondingly, the upregulation of PPAR-γ protein expression by PB2 in pressure-overloaded hearts was also counteracted by GW9662 co-administration. In conclusion, this study demonstrates that PB2 exerts protective effects against pathological cardiac fibrosis and inflammation through a PPAR-γ dependent mechanism.</p>","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458133","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":"Deciphering the Role of In-hospital Bleeding in Acute Coronary Syndromes.","authors":"Felice Gragnano, Paolo Calabrò, Dominick J Angiolillo","doi":"10.1097/FJC.0000000000001685","DOIUrl":"https://doi.org/10.1097/FJC.0000000000001685","url":null,"abstract":"","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143440867","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":"Decastatin, a novel Non-Collagenous 1 domain from collagen type X, harbors a specific fragment with antiangiogenic properties.","authors":"Stine Marie Jansen, Rastislav Pitek, Morten Asser Karsdal, Kim Henriksen","doi":"10.1097/FJC.0000000000001683","DOIUrl":"10.1097/FJC.0000000000001683","url":null,"abstract":"<p><p>The NC1 domains of collagens have been shown to possess antiangiogenic potential and, therefore, are of therapeutic interest for cancer. However, endostatin and other NC1 domains have not been successful in clinical tests. Therefore, we used evolutionary conservation to perform molecular deconstruction of the domains to further understand their structure-activity relationship, thereby deciphering their antiangiogenic potential. Homology exploration revealed that collagen type X contains a highly interesting NC1 domain (decastatin), with several sequences showing significant homology with vastatin, which is a known collagen type VIII-derived NC1 domain. For comparison, endostatin and vastatin were split into fragments, some of which contained highly conserved regions. The testing of these peptides revealed that the peptides containing conserved regions induced signaling, and fragment four of decastatin showed the highest potency of all fragments, with a calculated IC 50 value of 2.7 μM in the human umbilical vein endothelial cell (HUVEC)-based tube formation assay, which is like that of an intact NC1 domain. Notably, the corresponding fragment from vastatin (V4) also inhibited tube formation, suggesting that this region is of therapeutic interest. In summary, we used evolutionary conservation to identify a novel NC1 domain of collagen type X, a collagen playing a role in angiogenesis of the growth plate. Furthermore, we provided data indicating that the antiangiogenic activity of NC1 domain-derived peptides reside within their conserved domains. As a result, we identified a fragment called Decastatin fragment 4 (D4) derived from the NC1 domain of collagen type X, and which has potent antiangiogenic activity.</p>","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143399263","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":"Role of Indobufen in coronary artery disease: the story of a neglected drug. A systematic review.","authors":"Martino Pepe, Rocco Tritto, Gianluigi Napoli, Salvatore Giordano, Roberta Romito, Giuseppe Biondi-Zoccai, Nicola Corcione, Plinio Cirillo, Marco Matteo Ciccone","doi":"10.1097/FJC.0000000000001681","DOIUrl":"https://doi.org/10.1097/FJC.0000000000001681","url":null,"abstract":"<p><p>The management of antiplatelet therapy in coronary artery disease (CAD) is one of the most debated topics in cardiology. In some clinical scenarios, such as acute coronary syndromes (ACS) and/or percutaneous coronary interventions (PCI), a dual antiplatelet therapy (DAPT) based on the association of a thromboxane A2 (TXA2) pathway inhibitor and a P2Y12 inhibitor is required. Nevertheless, the recent research has been largely focused on the P2Y12 inhibitors, while few data are available on the TXA2 pathway inhibitors, besides aspirin. This gap in the evidence can have relevant clinical implications when aspirin is contraindicated. After years of empirical use, recent clinical studies have shed some light on the efficacy/safety profile of indobufen when compared to aspirin in low-risk CAD patients. However, also encouraged by promising pharmacodynamic data on platelet inhibition, further clinical investigations are strongly advocated.</p>","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143399265","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":"Impact of In-Hospital Bleeding on Post-Discharge Therapies and Prognosis in Acute Coronary Syndromes.","authors":"Luigi Spadafora, Matteo Betti, Fabrizio D'Ascenzo, Gaetano De Ferrari, Ovidio De Filippo, Carlo Gaudio, Carlos Collet, Pierre Sabouret, Pierfrancesco Agostoni, Carlo Zivelonghi, Bianca Pernice, Gianmarco Sarto, Beatrice Simeone, Erica Rocco, Federico Russo, Salvatore Giordano, Nicola Pierucci, Alberto Testa, Stefano Cacciatore, Giuseppe Biondi-Zoccai, Marco Bernardi","doi":"10.1097/FJC.0000000000001678","DOIUrl":"https://doi.org/10.1097/FJC.0000000000001678","url":null,"abstract":"<p><p>Acute coronary syndromes (ACS) continue to pose significant challenges for clinical practitioners, particularly regarding the prediction of mid- to long-term outcomes. This study aims to investigate the impact of in-hospital bleeding (IHB) at one-year follow-up in patients admitted for ACS. Data from 23,270 patients enrolled in the international PRAISE registry and discharged after ACS were analyzed. A total of 1,060 patients experienced IHB, while 18,765 did not; 3,445 were excluded due to missing data. The primary endpoint was all-cause mortality at 1 year. Secondary endpoints included major bleeding, reinfarction, and composite endpoints at 1 year. Patients with IHB were older, more frequently female, and had a higher prevalence of cardiovascular risk factors (all p < 0.05). At discharge, IHB patients were less likely to receive optimal medical therapy. At the one-year follow-up, all-cause mortality, major bleeding, and reinfarction were significantly higher in the IHB group (all p < 0.001). Bivariate analysis showed a strong association between IHB and all the outcomes of interest (all OR > 1; all p < 0.001). These associations remained significant even after adjusting for several covariates, except for reinfarction (OR 1.3; 95% CI 0.9-2.11; p = 0.149). Age, female sex, hypertension, and peripheral artery disease were found to be independent predictors of IHB, while DES implantation, radial access and left ventricular ejection fraction were identified as protective factors. IHB is a hallmark of frailty in ACS patients; therefore, greater attention should be given during follow-up to patients experiencing this condition.</p>","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143390848","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":"SGLT2 Inhibitors in the Elderly: Redefining Cardiac Care Beyond Age.","authors":"Marco Giuseppe Del Buono, Simone Filomia, Gianluigi Saponara, Tommaso Sanna","doi":"10.1097/FJC.0000000000001680","DOIUrl":"https://doi.org/10.1097/FJC.0000000000001680","url":null,"abstract":"","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143390853","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":"Relationship between ALDH2 Gene Polymorphism and Vasodilative Effect of Nitroglycerin on Coronary Arteries.","authors":"Kai Zhang, Chi He, Yaliang Tong, Yuquan He","doi":"10.1097/FJC.0000000000001682","DOIUrl":"https://doi.org/10.1097/FJC.0000000000001682","url":null,"abstract":"<p><p>Aldehyde dehydrogenase 2 (ALDH2) is a key enzyme that facilitates the biological metabolism of nitroglycerin. However, no study investigated the association between ALDH2 gene polymorphism and the vasodilation of coronary arteries following intracoronary administration of nitroglycerin. In the present study, we enrolled 427 patients with suspected angina pectoris. ALDH2 genotyping was performed and all patients were given 200 µg nitroglycerin in the right coronary artery during the coronary angiography. The invasive hemodynamic parameters including systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR) were monitored. The reference diameter and stenosis diameter of the right coronary artery were measured with the Stenosis Analysis 1.6 software. Both wild-type and mutant-type groups exhibited significant decreases in SBP, DBP values and increases in HR value after administration of nitroglycerin (P < 0.05). The wild-type group showed significantly higher absolute difference values in SBP when compared to the mutant-type group (P < 0.05). The mutant-type group exhibited significantly lower difference values and rates of change in reference diameter compared to the wild-type group (0.3±0.3 vs. 0.5±0.2, P < 0.001 for the difference value of diameter; 9.6±9.5 vs. 15.8±8.5, P < 0.001 for the rate of change (%)). Conversely, no differences were observed between the wild-type and mutant-type groups in terms of the difference value and rate of change of the stenosis diameter (P > 0.05). In conclusion, ALDH2 gene polymorphism (Glu504Lys) is associated with changes in invasive hemodynamic parameters and coronary artery diameter after intracoronary injection of nitroglycerin.</p>","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143390850","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":"A Game Changer for Resistant Hypertension: The Rise of Aprocitentan.","authors":"Ali H Eid","doi":"10.1097/FJC.0000000000001679","DOIUrl":"https://doi.org/10.1097/FJC.0000000000001679","url":null,"abstract":"<p><p>Hypertension is a major risk factor for cardiovascular disease (CVD), and a major contributor to global morbidity and mortality. In particular, resistant hypertension (rHTN), defined as blood pressure that remains elevated despite treatment with at least three antihypertensive agents including a diuretic, continues to be a major pharmacotherapeutic challenge. Traditional antihypertensive drugs often fail in patients with rHTN, underscoring the need for novel therapies. This is a brief mini-review of aprocitentan, a new drug that promises a glimmer of hope for rHTN patients. This drug is a dual endothelin (ET) receptor antagonist that blocks both ETA and ETB receptors. Given that these two receptors are critical players in vasotone regulation, antagonizing them, such as by aprocitentan, would be expected to significantly reduce blood pressure in patients with rHTN. Indeed, the PRECISION clinical trial demonstrated aprocitentan's superior effectiveness in reducing blood pressure in resistant patients, and the effects were sustained. Aprocitentan has been recently FDA-approved, marking a major milestone in hypertension management, offering hope for patients with difficult-to-treat hypertension.</p>","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143189579","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}