Vascular pharmacology最新文献

{"title":"Endostatin in disease modulation: From cancer to beyond","authors":"J. Anakha,&nbsp;Yenisetti Rajendra Prasad,&nbsp;Abhay H. Pande","doi":"10.1016/j.vph.2024.107459","DOIUrl":"10.1016/j.vph.2024.107459","url":null,"abstract":"<div><div>Angiogenesis plays a pivotal role in various pathological conditions, making it a key target in therapeutic development. Anti-angiogenic therapies are gaining traction for their potential in treating a range of angiogenesis-dependent diseases. Among these, endogenous angiogenesis inhibitors, particularly endostatin, have garnered significant attention for their therapeutic potential. While extensively studied for its anti-angiogenic effects in cancer, endostatin also exhibits anti-atherosclerotic and anti-fibrotic properties, broadening its therapeutic scope. Despite the successful clinical use of recombinant human endostatin in China for nearly two decades, its broader therapeutic potential remains underexplored. Thus, this review delves into the multifaceted applications of endostatin, examining its role in ocular diseases, inflammation, reproductive disorders, and tumor angiogenesis. Furthermore, it provides a comprehensive overview of its emerging roles beyond angiogenesis, particularly in the context of atherosclerosis and fibroproliferative conditions.</div></div>","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":"158 ","pages":"Article 107459"},"PeriodicalIF":3.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142873024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elucidating emerging signaling pathways driving endothelial dysfunction in cardiovascular aging","authors":"Anna De Bartolo ,&nbsp;Tommaso Angelone ,&nbsp;Carmine Rocca","doi":"10.1016/j.vph.2025.107462","DOIUrl":"10.1016/j.vph.2025.107462","url":null,"abstract":"<div><div>The risk for developing cardiovascular diseases dramatically increases in older individuals, and aging vasculature plays a crucial role in determining their morbidity and mortality. Aging disrupts endothelial balance between vasodilators and vasoconstrictors, impairing function and promoting pathological vascular remodeling. In this Review, we discuss the impact of key and emerging molecular pathways that transduce aberrant inflammatory signals (i.e.<em>,</em> chronic low-grade inflammation-inflammaging), oxidative stress, and mitochondrial dysfunction in aging vascular compartment. We focus on the interplay between these events, which contribute to generating a vicious cycle driving the progressive alterations in vascular structure and function during cardiovascular aging. We also discuss the primary role of senescent endothelial cells and vascular smooth muscle cells, and the potential link between vascular and myeloid cells, in impairing plaque stability and promoting the progression of atherosclerosis. The aim of this summary is to provide potential novel insights into targeting these processes for therapeutic benefit.</div></div>","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":"158 ","pages":"Article 107462"},"PeriodicalIF":3.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142979273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Kinome profiling: A veritable Rosetta Stone for protease-activated receptor 1 biased signaling","authors":"Rahul Rajala ,&nbsp;Courtney T. Griffin","doi":"10.1016/j.vph.2025.107469","DOIUrl":"10.1016/j.vph.2025.107469","url":null,"abstract":"","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":"158 ","pages":"Article 107469"},"PeriodicalIF":3.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143190635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lack of AMP-activated protein kinase-α1 reduces nitric oxide synthesis in thoracic aorta perivascular adipose tissue","authors":"Abdmajid Hwej ,&nbsp;Ali Al-Ferjani ,&nbsp;Yazeed Alshuweishi ,&nbsp;Abdullah Naji ,&nbsp;Simon Kennedy ,&nbsp;Ian P. Salt","doi":"10.1016/j.vph.2024.107437","DOIUrl":"10.1016/j.vph.2024.107437","url":null,"abstract":"<div><h3>Objective</h3><div>Perivascular adipose tissue (PVAT) releases anti-contractile bioactive molecules including NO. PVAT anti-contractile activity is attenuated in mice lacking AMPKα1 (AMP-activated protein kinase-α1). As AMPK regulates endothelial NO synthase (eNOS) activity in cultured cells, NO synthesis was examined in PVAT from AMPKα1 knockout (KO) mice.</div></div><div><h3>Methods and results</h3><div>Endothelium-denuded thoracic or abdominal aortic rings were isolated from wild type (WT) and KO mice. NOS inhibition enhanced vasoconstriction in PVAT-intact thoracic aortic rings from mice of either genotype yet had no effect on abdominal rings as assessed by wire myography. Thoracic aorta PVAT exhibited increased NO production, NOS activity and levels of the brown adipose tissue marker uncoupling protein-1 (UCP1) compared to abdominal PVAT. In KO mice, NO production was significantly reduced in thoracic but not abdominal PVAT. Reduced NO production in KO thoracic PVAT was not due to altered levels or phosphorylation of eNOS but was associated with increased caveolin-1:eNOS association and caveolin-1 Tyr14 phosphorylation. A peptide that disrupts eNOS:caveolin-1 association increased NO synthesis and reduced vasoconstriction of PVAT-intact thoracic but not abdominal aortic rings. KO thoracic PVAT also exhibited reduced UCP1 levels.</div></div><div><h3>Conclusions</h3><div>Murine thoracic aorta PVAT exhibits higher NO synthesis and UCP1 levels than abdominal aortic PVAT. Downregulation of AMPK suppresses NO synthesis which may contribute to the reduced anticontractile activity and reduced brown adipose tissue phenotype of KO thoracic PVAT. The mechanism underlying the effect of AMPK downregulation likely results from increased caveolin-1:eNOS association associated with caveolin-1 Tyr14 phosphorylation.</div></div>","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":"157 ","pages":"Article 107437"},"PeriodicalIF":3.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142476165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sotatercept: New drug on the horizon of pulmonary hypertension","authors":"Rosalinda Madonna,&nbsp;Filippo Biondi","doi":"10.1016/j.vph.2024.107442","DOIUrl":"10.1016/j.vph.2024.107442","url":null,"abstract":"<div><div>Sotatercept (brand name WINREVAIR, developed by Merck) is an activin receptor type IIA-Fc (ActRIIA-Fc), working by sequestering free activins. Sotatercept restores the balance between the activin proliferative pathway and the bone morphogenic protein (BMP) antiproliferative pathway in the pulmonary arterial cirulation. Sotatercept recently received approval in the USA and in Europe for the treatment of adults with pulmonary arterial hypertension (PAH) Group 1, on top of background PAH therapy to increase exercise capacity, improve WHO functional class and reduce the risk of clinical worsening events. Nevertheless, several studies are ongoing to investigate the potential adverse reactions of the drug especially at the haematological level. We provide an overview of the clinical and preclinical evidence of the targeting the activing pathway through sotatercept on the treatment of PAH. We also discuss what other possibilities there are for the application of sotatercept in the setting of pulmonary hypertension other than PAH Group 1.</div></div>","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":"157 ","pages":"Article 107442"},"PeriodicalIF":3.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142689032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional characterization of human IL-8 in vascular stenosis using a novel humanized transgenic mouse model","authors":"Wei Zhang ,&nbsp;Lihua Pan ,&nbsp;Xiaoliang Wu ,&nbsp;Orazio J. Slivano ,&nbsp;Kunzhe Dong ,&nbsp;Xiaochun Long","doi":"10.1016/j.vph.2024.107438","DOIUrl":"10.1016/j.vph.2024.107438","url":null,"abstract":"<div><div>IL-8 (aka interleukin 8, CXCL8) is a prototypic cytokine that is highly expressed in the diseased vessel wall and its plasma concentration is strongly associated with cardiovascular events. However, whether IL-8 plays a causative role in cardiovascular diseases remains largely unknown. In this study we used a human <em>IL-8</em> transgenic (Tg) mouse strain with a bacterial artificial chromosome (BAC) integrated into its genome. This BAC encompasses 166 kb of sequence encompassing the human <em>IL-8</em> gene locus as well as upstream and downstream DNA sequences containing regulatory elements. This BAC ensured a pathophysiologically regulated, rather than forced constitutive, expression of human <em>IL-8</em> in the mouse. Tg mice were subjected to complete carotid ligation injury. IL-8 was highly expressed in the ligation-injured carotid artery from 3 days until 2 weeks after injury. As a result, exacerbated neointimal hyperplasia and increased Mac2 and PCNA positive cells were observed in Tg mice. To further confirm its role in promoting neointimal formation, IL-8 was neutralized by anti-IL8 treatment at the ligation site. Consequently, the size of neointima was significantly reduced. Our results provided new insights into the regulation and function of IL-8 in response to vascular insult and during neointima formation.</div></div>","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":"157 ","pages":"Article 107438"},"PeriodicalIF":3.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142565027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of serum 25-hydroxyvitamin D3 levels with carotid artery intima-media thickness and carotid atherosclerotic plaques in smokers","authors":"Yongjian Liu ,&nbsp;Yongbin Pei ,&nbsp;Shuowen Zhang,&nbsp;Zhixing Du,&nbsp;Litao Chen,&nbsp;Xiaojing Yan ,&nbsp;Jin Tian","doi":"10.1016/j.vph.2024.107416","DOIUrl":"10.1016/j.vph.2024.107416","url":null,"abstract":"<div><h3>Objective</h3><p>This study explores the association of serum 25-hydroxyvitamin D3 (25(OH)D3) levels with carotid artery intima-media thickness (CIMT), and the presence of carotid atherosclerotic plaques in individuals with a history of smoking.</p></div><div><h3>Methods</h3><p>A total of 469 patients suspected of having carotid atherosclerosis, aged 52 to 73 years with an average age of 65.26 ± 4.37 years, were recruited from the author's hospital from January 2023 to October 2023. All patients had a smoking history of nearly 5 years. Based on their serum 25(OH)D3 levels, they were divided into two groups: the normal group (serum level 30–50 ng/mL, <em>n</em> = 300) and the deficiency group (&lt;30 ng/mL, <em>n</em> = 169). General details of the two patient groups were collected. Carotid artery ultrasound was employed to assess pulse wave velocity (PWV), carotid artery compliance coefficient (CC), and CIMT. Blood chemistry analysis measured serum lipid metabolism indicators including total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HD-LC). The relationship between CIMT and each variable was analyzed through Pearson correlation, and logistic regression was used to identify risk factors influencing carotid artery plaque development.</p></div><div><h3>Results</h3><p>General patient information between the two groups showed no significant differences (<em>P</em> &gt; 0.05). Patients in the 25(OH)D3 deficiency group exhibited elevated left and right PWV and CC compared to the 25(OH)D3 normal group (<em>P</em> &lt; 0.05). The deficiency group exhibited larger CIMT and plaque area compared to the normal group (<em>P</em> &lt; 0.05). Additionally, the deficiency group demonstrated higher levels of TC, LDL-C, and HD-LC compared to the normal group (<em>P</em> &lt; 0.05). A moderate positive correlation was found between TC, LDL-C, and CIMT (<em>P</em> &lt; 0.05), while a strong positive correlation existed between 25(OH)D3 and CIMT (P &lt; 0.05). In smokers, the formation of carotid artery plaque was associated with factors such as patient age, CIMT, serum LDL-C, and 25(OH)D3 levels (<em>P</em> &lt; 0.05). As age, CIMT, LDL-C levels increased, and 25(OH)D3 levels decreased, the risk of carotid plaques in smokers increased (<em>P</em> &lt; 0.05).</p></div><div><h3>Conclusions</h3><p>Smokers with lower 25(OH)D3 levels exhibit higher CIMT and more prominent carotid atherosclerotic plaques, indicating increased arterial stiffness and elevated cardiovascular risk. These findings demonstrate crucial implications that insufficient levels of vitamin D may potentially contribute to a higher risk of atherosclerosis among smokers.</p></div>","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":"157 ","pages":"Article 107416"},"PeriodicalIF":3.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141996565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gaps in evidence in the treatment of prevalent patients with pulmonary arterial hypertension at intermediate risk: An expert consensus","authors":"Giovanna Manzi ,&nbsp;Raymond L. Benza ,&nbsp;Paola Argiento ,&nbsp;Gavino Casu ,&nbsp;Marco Corda ,&nbsp;Michele Correale ,&nbsp;Michele D'Alto ,&nbsp;Giuseppe Galgano ,&nbsp;Andrea Garascia ,&nbsp;Stefano Ghio ,&nbsp;Mardi Gomberg-Maitland ,&nbsp;Massimiliano Mulé ,&nbsp;Giuseppe Paciocco ,&nbsp;Silvia Papa ,&nbsp;Daniele Prati ,&nbsp;Ioana R. Preston ,&nbsp;Claudia Raineri ,&nbsp;Emanuele Romeo ,&nbsp;Laura Scelsi ,&nbsp;Davide Stolfo ,&nbsp;Carmine Dario Vizza","doi":"10.1016/j.vph.2024.107432","DOIUrl":"10.1016/j.vph.2024.107432","url":null,"abstract":"<div><p>Despite the innovations introduced in the 2022 European Society of Cardiology/European Respiratory Society Guidelines on Pulmonary Hypertension, risk discrimination and management of pulmonary arterial hypertension (PAH) patients at intermediate risk still represents a grey zone. Additionally, clinical evidence derived from currently available studies is limited. This expert panel survey intends to aid physicians in choosing the best therapeutic strategy for patients at intermediate risk despite ongoing oral therapy. An expert panel of 24 physicians, specialized in cardiology and/or pulmonology with expertise in handling all drugs available for the treatment of PAH participated in the survey. All potential therapeutic options for patients at intermediate risk were explored and analyzed to produce graded consensus statements regarding: the switch from endothelin receptor antagonist (ERA) or phosphodiesterase 5 inhibitor (PDE5i) to another oral drug of the same class; the addition of a drug targeting the prostacyclin pathway administered by different routes; the switch from PDE5i to riociguat.</p></div>","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":"157 ","pages":"Article 107432"},"PeriodicalIF":3.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142241183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Altered copper transport in oxidative stress-dependent brain endothelial barrier dysfunction associated with Alzheimer's disease","authors":"Md. Selim Hossain ,&nbsp;Archita Das ,&nbsp;Ashiq M. Rafiq ,&nbsp;Ferenc Deák ,&nbsp;Zsolt Bagi ,&nbsp;Rashelle Outlaw ,&nbsp;Varadarajan Sudhahar ,&nbsp;Mai Yamamoto ,&nbsp;Jack H. Kaplan ,&nbsp;Masuko Ushio-Fukai ,&nbsp;Tohru Fukai","doi":"10.1016/j.vph.2024.107433","DOIUrl":"10.1016/j.vph.2024.107433","url":null,"abstract":"<div><div>Oxidative stress and blood-brain barrier (BBB) disruption due to brain endothelial barrier dysfunction contribute to Alzheimer's Disease (AD), which is characterized by beta-amyloid (Aβ) accumulation in senile plaques. Copper (Cu) is implicated in AD pathology and its levels are tightly controlled by several Cu transport proteins. However, their expression and role in AD, particularly in relation to brain endothelial barrier function remains unclear. In this study, we examined the expression of Cu transport proteins in the brains of AD mouse models as well as their involvement in Aβ42-induced brain endothelial barrier dysfunction. We found that the Cu uptake transporter CTR1 was upregulated, while the Cu exporter ATP7A was downregulated in the hippocampus of AD mouse models and in Aβ42-treated human brain microvascular endothelial cells (hBMECs). In the 5xFAD AD mouse model, Cu levels (assessed by ICP-MS) were elevated in the hippocampus. Moreover, in cultured hBMECs, Aβ42-induced reactive oxygen species (ROS) production, ROS-dependent loss in barrier function (measured by transendothelial electrical resistance), and tyrosine phosphorylation of CDH5 were all inhibited by either a membrane permeable Cu chelator or by knocking down CTR1 expression. These findings suggest that dysregulated expression of Cu transport proteins may lead to intracellular Cu accumulation in the AD brain, and that Aβ42 promotes ROS-dependent brain endothelial barrier dysfunction and CDH5 phosphorylation in a CTR1-Cu-dependent manner. Our study uncovers the critical role of Cu transport proteins in oxidative stress-related loss of BBB integrity in AD.</div></div>","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":"157 ","pages":"Article 107433"},"PeriodicalIF":3.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142322361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Examining the controversies in venous thromboembolism prophylaxis for vascular surgery patients: A critical review","authors":"Tao Fang,&nbsp;Ran Zhang,&nbsp;Yanmei Li","doi":"10.1016/j.vph.2024.107436","DOIUrl":"10.1016/j.vph.2024.107436","url":null,"abstract":"<div><h3>Background</h3><div>Venous thromboembolism (VTE) is a significant concern in vascular surgery due to its potentially severe consequences. Effective prophylactic measures are essential to minimize the risks associated with VTE. However, considerable controversy remains regarding the optimal strategies for VTE prevention in patients undergoing vascular procedures.</div></div><div><h3>Methods</h3><div>This review critically analyzes key clinical research, guidelines, and expert opinions to explore the advantages and limitations of various VTE prophylaxis approaches. The pharmacological and mechanical methods are explored, with a focus on balancing the risk of VTE against the potential for bleeding complications, particularly in high-risk patients.</div></div><div><h3>Results</h3><div>The review addresses controversial issues such as the choice of anticoagulants, dosage, timing, and duration of prophylaxis. The lack of consensus in existing guidelines and the variability in clinical practice regarding VTE prevention in vascular surgery patients is highlighted. The role of patient-specific risk factors, including the use of intraoperative anticoagulation and bleeding risks, is also examined.</div></div><div><h3>Conclusion</h3><div>This review provides a comprehensive evaluation of VTE prophylaxis strategies in vascular surgery, emphasizing the need for individualized, evidence-based approaches. Clarifying these controversies is crucial for optimizing patient outcomes and minimizing both thrombotic and hemorrhagic complications.</div></div>","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":"157 ","pages":"Article 107436"},"PeriodicalIF":3.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142476208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}