European Atherosclerosis Journal最新文献

{"title":"Role of histone deacetylase 3 (HDAC3) in adipose tissue metabolism and immunophenotype: Selected Abstract - SITeCS Congress 2022","authors":"L. Coppi, C. Peri, F. Bonacina, R. Longo, Dalma Cricrí, S. Pedretti, Rui Silva, I. Severi, A. Giordano, G. Norata, A. Catapano, N. Mitro, E. De Fabiani, M. Crestani","doi":"10.56095/eaj.v1i3.22","DOIUrl":"https://doi.org/10.56095/eaj.v1i3.22","url":null,"abstract":"Introduction: Obesity is associated with comorbidities such as cardiovascular disease and type 2 diabetes. HDAC3 regulates adipose tissue physiology (WAT), and its genetic inactivation causes metabolic reprogramming of white adipocytes toward browning. The aim of this work is to evaluate the effect of HDAC3 silencing at different stages of differentiation and investigate the influence of adipocyte metabolism on the immunophenotype of WAT. Materials and Methods: Following HDAC3 silencing in mesenchymal stem cells and mature adipocytes, adipocyte function, RNA, DNA and protein levels, and proliferation at the end of differentiation were analyzed. Visceral WAT immunophenotype (vWAT) of Hdac3 KO mice in WAT (Hdac3fatKO) and controls (FL) was performed by FACS. Results: Silencing HDAC3 in precursors amplifies the expression of genes and proteins that regulate differentiation, oxidative metabolism, browning and mitochondrial activity. Following silencing, we found increased 1)phosphorylation of AKT (1.64 fold change, P<0.0001), indicative of increased insulin signaling, and 2)proliferation, characteristic of the early phase of differentiation. Mitochondrial content was unchanged, but increased mitochondrial activity was observed in terms of maximal respiration (1.42 fold change, P=0.0151) and uncoupling of the electron transport chain (+11.6%, P<0.0001). No difference was observed following HDAC3 silencing in mature adipocytes. We hypothesized that the enhancement of oxidative metabolism may cause cellular damage or senescence and, consequently, the immunophenotype of vWAT might be affected by HDAC3 ablation. Analysis reveals an increase of macrophages (2.48 fold change, P=0.0311) in the vWAT of Hdac3fatKO mice polarizing toward the M2 population. Coculture of adipocytes with macrophages from bone marrow indicates that HDAC3 silencing in adipocytes stimulates macrophage activation. Conclusions: HDAC3 is a key factor in the WAT phenotype, and its inactivation triggers mechanisms that support browning. Early epigenetic events mediated by HDAC3 silencing are crucial in directing adipocyte precursors toward the oxidative phenotype. Finally, results obtained from ex vivo and in vitro studies suggest that specific factors produced by KO adipocytes may be involved in determining the observed immunophenotype. [FONDAZIONE CARIPLO 2015-0641]","PeriodicalId":227903,"journal":{"name":"European Atherosclerosis Journal","volume":"7 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"131503981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of the deletion of prenylcysteine-oxidase 1 (PCYOX1) on arterial thrombosis in an animal model: Selected Abstract - SITeCS Congress 2022","authors":"P. Amadio, C. Banfi, M. Zarà, M. Brioschi, S. Ghilardi, L. Sandrini, S. Barbieri","doi":"10.56095/eaj.v1i3.19","DOIUrl":"https://doi.org/10.56095/eaj.v1i3.19","url":null,"abstract":"Prenylcysteine-oxidase1 (PCYOX1) enzyme, involved in the degradation of prenylated proteins, is expressed in different types of cells, among which vascular and blood cells. Previous studies demonstrated that the secretome of cells silenced for PCYOX1 reduced platelet adhesion on both fibrinogen and endothelial cells, suggesting its possible involvement in thrombotic mechanisms.  In this study we analyzed the role of PCYOX1 in arterial thrombosis by the use of an animal model. All the procedures have been carried on mice knock-out for PCYOX1 (Pcyox1KO) that were compared with wild-type (WT) mice. Arterial thrombosis was induced by Ferric chloride application on carotid artery, while pulmonary thromboembolism was induced by the injection of collagen-epinephrine. The phenotype and the functionality of platelets were analyzed by cytofluorimetry and functional tests. The expression of PCYOX1 on platelets was evaluated by mass spectrometry.  Thrombus formation induced by Ferric Chloride was reduced in Pcyox1KO mice, that were also protected from pulmonary thromboembolism. No differences were identified in blood cells count, vascular pro-coagulant activity and functional fibrinogen. Interestingly, Pcyox1KO mice displayed a marked reduction in the number of platelets-leukocytes aggregates, in the release of alpha granules, in the activation of receptor αIIbβ3 and in platelets aggregation induced by ADP e TRAP (analyzed on whole blood or platelets rich plasma). Mass spectrometry showed that PCYOX1 was highly expressed in WT platelets. However, the deletion of PCYOX1 did not alter platelets phosphorylation pathways, and platelets adhesion and aggregation (analyzed on washed platelets), in respect of WT mice. Of note, when platelets aggregation was performed on washed platelets isolated from WT mice in the presence of plasma derived from Pcyox1KO mice, we observed a strong impairment in comparison with the aggregation obtained on the same platelets resuspended in plasma derived from WT mice.  In conclusion, our results, showing an ipo-reactivity of platelets and a reduced arterial and pulmonary thrombosis in Pcyox1KO mice, suggest that this protein could represent a new potential target in antithrombotic therapy.","PeriodicalId":227903,"journal":{"name":"European Atherosclerosis Journal","volume":"77 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"115145102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"European, Russian and American Clinical Guidelines on dyslipidemias management – where do we stand? European, Russian, and US guidelines on dyslipidemias","authors":"A. Alieva, E. Usova, O. Reutova","doi":"10.56095/eaj.v1i2.14","DOIUrl":"https://doi.org/10.56095/eaj.v1i2.14","url":null,"abstract":"Current clinical guidelines on lipid metabolism disorders are represented by the integration of relevant multicenter observational studies and registries aimed to identify best strategies in cardiovascular risk stratification, diagnostics and treatment of dyslipidemias. The approaches outlined in the European, Russian and American clinical guidelines look relevant to each other despite a range slightly different postulates, as they all demonstrate a general tendency to the importance of accurate risk stratification of patients and timely action on low-density lipoprotein cholesterol (LDL-C) levels when using effective lipid-lowering therapy.","PeriodicalId":227903,"journal":{"name":"European Atherosclerosis Journal","volume":"55 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"126712714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FindMyLipidClinic.com: A global Directory of lipid clinics and patient organisations to improve dyslipidemia care: FindMyLipidClinic.com","authors":"C. Stevens, A. Lyons, Kanika I Dharmayat, J. Brandts, A. Vallejo-Vaz, Magdalena Daccord, K. Ray","doi":"10.56095/eaj.v1i2.11","DOIUrl":"https://doi.org/10.56095/eaj.v1i2.11","url":null,"abstract":"Information available on lipid clinics and patient support and advocacy groups, such as location and services provided, is limited or unknown to patients with dyslipidaemia and their family members who may also be affected, and non-specialist clinicians, hindering accessibility to appropriate healthcare. To overcome this, the European Atherosclerosis Society Familial Hypercholesterolemia Study Collaboration (EAS FHSC) led by Imperial College London has, in collaboration with the European FH Patient Network (FH Europe), developed FindMyLipidClinic.com, a global Directory of lipid clinics and patient support groups in 29 languages. Since its launch in 2020, around 4,000 visitors have conducted 12,000 searches across 1,100 locations, which may have retrieved up to 124 lipid clinics and 29 patient groups currently listed in 39 and 28 countries, respectively. Clinics and patient organisations not currently listed are encouraged to join this directory, and it would also benefit further from collaborations with other existing directories able to contribute. ","PeriodicalId":227903,"journal":{"name":"European Atherosclerosis Journal","volume":"17 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"130980397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic impact of extrahepatic PCSK9 modulation: Extrahepatic PCSK9 modulation","authors":"L. Da Dalt, F. Bonacina","doi":"10.56095/eaj.v1i2.13","DOIUrl":"https://doi.org/10.56095/eaj.v1i2.13","url":null,"abstract":"The Proprotein Convertase Subtilisin Kexin type 9 (PCSK9) protease is a 692 amino acid glycoprotein which belongs to the proprotein convertase family. PCSK9 binds several receptors of the LDL family, including VLDLR, LRP1 but also with CD36, driving their lysosomal degradation. From the beginning of the 21st century a growing body of interest raised around the opportunity to pharmacologically inhibit PCSK9, and most recently, monoclonal antibodies have been successfully tested for the treatment of severe/genetic forms of dyslipidemia. Despite the majority of circulating PCSK9 being produced by the liver, other organs come into play contributing to its production, such as the heart, the pancreas, and the brain. Nonetheless, extrahepatic PCSK9 may exert a local/paracrine and or autocrine metabolic impact in the homeostatic regulation of cholesterol metabolism, suggesting that, opposite to the liver, in other tissue PCSK9 deficiency or inhibition could contribute to the development of specific organ and tissues dysfunctionalities.","PeriodicalId":227903,"journal":{"name":"European Atherosclerosis Journal","volume":"20 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"124378038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lipid-lowering for the prevention of cardiovascular disease in the new era: A practical approach to combination therapy: Lipid-lowering and combination therapy","authors":"E. Michos, K. Ferdinand","doi":"10.56095/eaj.v1i1.9","DOIUrl":"https://doi.org/10.56095/eaj.v1i1.9","url":null,"abstract":"Low density lipoprotein-cholesterol (LDL-C) is the main etiologic factor for the development and progression of atherosclerotic cardiovascular disease (ASCVD) and LDL-C reduction is a central tenet of ASCVD treatment and prevention. Moreover, ASCVD risk reduction is proportional to the magnitude of LDL-C lowering. Recent European guidelines have recommended a goal of <55 mg/dL (<1.4 mmol/L) for patients at very-high cardiovascular risk, while the U.S. guideline considers an LDL-C ≥70 mg/dL (≤1.8 mmol/L) as a threshold to intensify therapy with the addition of a non-statin therapy to statins. To reach these lower LDL-C goals of <55 mg/dL or <70 mg/dL, combination therapy is necessary in the majority of these patients. Drug combinations, and in particular single-pill combinations, may substantially increase adherence to therapy. Adherence is essential for achieving a clinical benefit and, as many patients discontinue medications, the long-term adherence to lipid-lowering therapy represents a major issue in ASCVD prevention. Secondary prevention or high-risk primary prevention patients, such as those with familial hypercholesterolemia in whom maximally-tolerated statin doses alone would not be anticipated to sufficiently lower LDL-C, would benefit from combination therapy. In current clinical practice, statins with ezetimibe, statins plus PCSK9 inhibitors (with or without ezetimibe), and, most recently statins or ezetimibe with bempedoic acid are the most commonly used combination therapies for LDL-C-lowering. This review outlines the importance of using combination therapy for the achievement of LDL-C treatment","PeriodicalId":227903,"journal":{"name":"European Atherosclerosis Journal","volume":"29 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"132049847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combination therapy in the guidelines: from high-intensity statins to high-intensity lipid-lowering therapies: Combination therapy in the guideline","authors":"L. Masana, D. Ibarretxe, N. Andreychuk, M. Royuela, C. Rodríguez-Borjabad, N. Plana","doi":"10.56095/eaj.v1i1.10","DOIUrl":"https://doi.org/10.56095/eaj.v1i1.10","url":null,"abstract":"The causal role of cholesterol in atherosclerosis was established more than 100 years ago. Along with the fact that the higher the cholesterol, the greater the risk of atherosclerotic cardiovascular diseases (ASCVD), many randomized controlled trials (RCT) have shown that lowering LDL cholesterol (LDL-C) is associated with a lower incidence of ASCVD. This impact of lipid-lowering therapies on cardiovascular risk is independent of the drug used, as shown by several meta-analyses and Mendelian randomization studies. Therefore, the concept of using “high-intensity statins” should be changed to “high-intensity lipid-lowering therapies” that go beyond the use of statins. Recent RCTs using non-statin lipid-lowering therapies has provided scientific evidence that the lower the LDL-C, the better in terms of cardiovascular events. Based on these observations, current guidelines recommend achieving very low LDL-C levels in patients with high and very-high cardiovascular risk. To achieve these demanding goals, the physician must use the full spectrum of lipid-lowering therapies, beyond high-intensity, high-dose statins. Oral combination therapies and, when necessary, subcutaneous treatments become the new standard of care for hypercholesterolemia. However, the number of patients achieving LDL-C goals is unacceptably low. This is due in part to insufficient prescription and insufficient treatment. To improve the efficacy of therapy, several strategies have been proposed, step by step, planning therapy and maximizing treatment, based on the needs of the patient. A wider use of lipid-lowering","PeriodicalId":227903,"journal":{"name":"European Atherosclerosis Journal","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"125899224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cholesterol-lowering drugs: Focus on Ezetimibe: Cholesterol-lowering drugs: Focus on ezetimibe","authors":"H. Bays","doi":"10.56095/eaj.v1i1.8","DOIUrl":"https://doi.org/10.56095/eaj.v1i1.8","url":null,"abstract":"Ezetimibe is an intestinal cholesterol/sterol inhibitor. It is generally well-tolerated, and except for coadministration with cyclosporin (which increases concentration of both ezetimibe and cyclosporin), has limited drug interactions. Clinical trial data suggests that ezetimibe 10 mg orally once a day reduces low density lipoprotein cholesterol (LDL-C) levels about 15-25% as monotherapy or when added to statins, depending on the patient and individual clinical trial. Ezetimibe also reduces lipoprotein remnants. Due to its additive effects to statins, international lipid guidelines recommend ezetimibe as an option for patients who do not achieve LDL-C treatment goals with statins alone. The Improved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT) trial demonstrated that when added to statin therapy, ezetimibe incrementally lowered LDL-C levels and modestly improved cardiovascular outcomes. Ezetimibe is formulated as monotherapy, or as a fixed-dose combination with statins or bempedoic acid. Finally, ezetimibe is the only pharmacotherapy approved for treatment of beta-sitosterolemia, which is a rare autsomal recessive disorder resulting in enhanced intestinal cholesterol absorption, increased circulating sterols, and tendinous and cutaneous xanthomas, arthritis or arthralgia, and premature cardiovascular disease.","PeriodicalId":227903,"journal":{"name":"European Atherosclerosis Journal","volume":"73 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"116031100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The pharmacology of cholesterol-lowering drugs: The pharmacology of cholesterol-lowering drugs","authors":"C. Ballantyne, A. Catapano","doi":"10.56095/eaj.v1i1.7","DOIUrl":"https://doi.org/10.56095/eaj.v1i1.7","url":null,"abstract":"The causal role of low-density lipoprotein cholesterol LDL-C in atherosclerotic-related cardiovascular disease (ASCVD) has been undoubtedly established over the last decades, and lowering plasma LDL-C levels represents the main approach to reduce the risk of cardiovascular (CV) events. A large number of observations has definitely proven that the protective effect is independent of the drug used to lower LDL-C, with a continuous linear reduction of CV risk with further LDL-C reductions. Although high-intensity statin therapy may significantly reduce CV event incidence, frequently statins are insufficient to achieve the large reductions recommended by current guidelines for high and very high risk patients. Several non-statin drugs, having mechanisms of action complementary to that of statins, are now available, and include ezetimibe, monoclonal antibodies targeting PCSK9, and, more recently, inclisiran, bempedoic acid, and evinacumab. Combining these drugs based on the recommendations by current and future guidelines should be considered for optimal risk reduction, although several gaps in clinical practice remain to be filled.","PeriodicalId":227903,"journal":{"name":"European Atherosclerosis Journal","volume":"22 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"115544878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}