{"title":"Eficacia, beneficio y seguridad de inclisiran","authors":"José López-Miranda","doi":"10.1016/j.arteri.2024.07.003","DOIUrl":"10.1016/j.arteri.2024.07.003","url":null,"abstract":"<div><div>Hypercholesterolemia is a causal factor of atherosclerotic cardiovascular disease (ASCVD), which is one of the main causes of morbidity and mortality in Spain. The reduction of LDL cholesterol (LDL-C) decreases the risk of ASCVD and adverse cardiovascular events. Targeted therapy for the proprotein convertase subtilisin/kexin type 9 (PCSK-9) has emerged as a novel tool for the treatment of hyperlipidemia. Inclisiran is a small double-stranded small interfering RNA that acts by blocking PCSK-9 transcription in hepatocytes, leading to a marked and sustained reduction in circulating LDL-C levels. In contrast to other lipid-lowering therapies such as statins, ezetimibe and monoclonal antibodies PCSK-9 inhibitors, Inclisiran proposes an infrequent dosing regimen of twice times a year. Its prolonged effect represents an advantage over non-compliance of the treatment, which is one of the main reasons why LDL-C goals are not achieved with standard therapy. This review aims to present and discuss current scientific data regarding the efficacy, tolerability and safety of Inclisiran in the treatment of hypercholesterolemia. Inclisiran has been shown to provide significant long-term reductions in LDL-C levels associated with notable decreases in levels of PCSK9 and other atherogenic lipoproteins with a highly favourable side effect profile similar to placebo. The convenience of a twice-yearly dosing regimen promotes adherence to therapy and facilitates achievement of LDL-C goals. Results from ongoing trials designed to determine its effect on cardiovascular events are expected to provide further information about the cardiovascular benefit of inclisiran in patients with ACVD and in patients at high cardiovascular risk.</div></div>","PeriodicalId":45230,"journal":{"name":"Clinica e Investigacion en Arteriosclerosis","volume":"36 ","pages":"Pages S24-S30"},"PeriodicalIF":1.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142792570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Nuevos fármacos para tratar las dislipemias. De las pequeñas moléculas a los ARN pequeños de interferencia","authors":"Lluís Masana, Daiana Ibarretxe","doi":"10.1016/j.arteri.2024.07.004","DOIUrl":"10.1016/j.arteri.2024.07.004","url":null,"abstract":"<div><div>Despite the various therapeutic tools available, many patients do not achieve therapeutic goals, and cardiovascular diseases remain a significant cause of death in our setting. Furthermore, even in patients who manage to reduce their LDL-C levels to the recommended targets, cardiovascular events continue to occur.</div><div>The therapeutic challenge and the persistent risk have led to active research into new drugs targeting novel therapeutic pathways in the field of lipoprotein metabolism disorders. The therapeutic approach involves new pharmacological mechanisms, ranging from small molecules and monoclonal antibodies to RNA interference, with inclisiran being the first drug approved for clinical use in the cardiovascular domain.</div><div>In this review, we aim to provide a comprehensive overview of the new therapeutic targets and pharmacological mechanisms under development, as well as their potential clinical impact.</div></div>","PeriodicalId":45230,"journal":{"name":"Clinica e Investigacion en Arteriosclerosis","volume":"36 ","pages":"Pages S15-S23"},"PeriodicalIF":1.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142792607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ovidio Muñiz-Grijalvo , Agustín Blanco Echevarría , María José Ariza Corbo , José Luis Díaz-Díaz
{"title":"Quilomicronemia multifactorial: claves para la detección de las formas severas","authors":"Ovidio Muñiz-Grijalvo , Agustín Blanco Echevarría , María José Ariza Corbo , José Luis Díaz-Díaz","doi":"10.1016/j.arteri.2024.11.003","DOIUrl":"10.1016/j.arteri.2024.11.003","url":null,"abstract":"<div><div>Multifactorial chylomicronemia associated with multiple comorbidities, drugs and habits is much more common than familial chylomicronemia, an autosomal recessive disease that can be considered as “rare disease”. Like the rest of hypertriglyceridemias, chylomicronemias could be classified as primary or monogenic and secondary in which, on the basis of polygenic predisposition, there is concomitant exposure to multiple triggering factors. In this brief revision, we will review its causes and management as well as the keys to its differential diagnosis of the Multifactorial Chylomicronemia.</div></div>","PeriodicalId":45230,"journal":{"name":"Clinica e Investigacion en Arteriosclerosis","volume":"36 ","pages":"Pages S13-S17"},"PeriodicalIF":1.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142822728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Javier Espíldora-Hernández , Tania Díaz-Antonio , Jesús Olmedo-Llanes , Jesús Zarzuela León , José Rioja , Pedro Valdivielso , Miguel Ángel Sánchez-Chaparro , María José Ariza
{"title":"Caracterización clínica y detección de arteriosclerosis subclínica en sujetos con hiperalfalipoproteinemia extrema","authors":"Javier Espíldora-Hernández , Tania Díaz-Antonio , Jesús Olmedo-Llanes , Jesús Zarzuela León , José Rioja , Pedro Valdivielso , Miguel Ángel Sánchez-Chaparro , María José Ariza","doi":"10.1016/j.arteri.2024.03.005","DOIUrl":"10.1016/j.arteri.2024.03.005","url":null,"abstract":"<div><h3>Introduction and objectives</h3><div>The association between HDL cholesterol (HDL-C) levels and death from cardiovascular disease follows a U-shaped pattern, increasing at the extremes. The objective of the study was to characterize a sample of subjects with extreme hyperalphalipoproteinemia (HAE).</div></div><div><h3>Material and methods</h3><div>53 cases with HAE were recruited, 24 women (HDL-C<!--> <!-->><!--> <!-->135<!--> <!-->mg/ dL) and 29 men (HDL-C<!--> <!-->><!--> <!-->116<!--> <!-->mg/ dL). A detailed medical history was taken and questionnaires on adherence to the Mediterranean diet and physical activity were collected. Carotid ultrasounds were performed to detect the presence of suclinical atherosclerosis.</div></div><div><h3>Results</h3><div>The most prevalent cardiovascular risk factor (CVRF) was dyslipidemia (64%) with no significant differences between men and women, unlike hypertension (21% in women, versus 55% in men, p<!--> <!-->=<!--> <!-->0.01) and others CVRF, for example, diabetes. 7% of the series had previous cardiovascular disease, women had higher LDL cholesterol (p<!--> <!-->=<!--> <!-->0.002) and HDL-C than men (without significant differences). Plaque was detected in 53% of cases, being more prevalent in men. Patients with plaque were older, drank more alcohol and smoked more (p<!--> <!--><<!--> <!-->0.05).</div></div><div><h3>Conclusions</h3><div>Men had a higher prevalence of CVRF than women, except for dyslipidemia. Subclinical atherosclerosis occurred in more than half of the series. Age, alcohol consumption and smoking were independently associated with the presence of plaque, however, our data do not show a significant influence of HDL-C levels.</div></div>","PeriodicalId":45230,"journal":{"name":"Clinica e Investigacion en Arteriosclerosis","volume":"36 6","pages":"Pages 325-332"},"PeriodicalIF":1.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140868402","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":"Risk factors and assessment of subclinical atherosclerosis in patients with psoriatic arthritis","authors":"Zhoulan Zheng , Qianru Liu , Zhenan Zhang , Qianyu Guo , Liyun Zhang , Gailian Zhang","doi":"10.1016/j.arteri.2024.04.001","DOIUrl":"10.1016/j.arteri.2024.04.001","url":null,"abstract":"<div><h3>Objective</h3><div>To understand the prevalence of subclinical atherosclerosis (SCA) in psoriatic arthritis (PsA) patients; to explore the correlation between PsA combined with SCA and traditional cardiovascular risk factors and disease activity; to compare the role of Framingham Risk Score (FRS) and atherosclerotic cardiovascular disease (ASCVD) scores.</div></div><div><h3>Methods</h3><div>We included 50 PsA patients who met the CASPAR classification criteria, 50 diabetes patients and 50 healthy people. Clinical data were collected from all patients, minimal disease activity (MDA), disease activity index for psoriatic arthritis (DAPSA), ASCVD, FRS were assessed in patients with PsA, and carotid artery intima–media thickness was measured.</div></div><div><h3>Results</h3><div>The prevalence of SCA in PsA patients was significantly higher than that in healthy controls (44% vs 24%, <em>P</em> <!--><<!--> <!-->0.05). Smoking, drinking, ASCVD, FRS were the risk factors of PsA with SCA (<em>P</em> <!--><<!--> <!-->0.05). Psoriasis (PsO) duration, PtGA, VAS and DAPSA were the risk factors for PsA with SCA (<em>P</em> <!--><<!--> <!-->0.05). FRS and ASCVD scores underestimated SCA risk in PsA patients.</div></div><div><h3>Conclusion</h3><div>Compared with healthy controls, patients with PsA have higher prevalence of SCA. High DAPSA is a risk factor for PsA with SCA. Carotid ultrasound can monitor SCA in patients with PsA, improve stratification of cardiovascular risk.</div></div>","PeriodicalId":45230,"journal":{"name":"Clinica e Investigacion en Arteriosclerosis","volume":"36 6","pages":"Pages 333-340"},"PeriodicalIF":1.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142548223","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}
María del Carmen López de las Hazas , Joao Tomé-Carneiro , Livia Balaguer , Gema de la Peña , Luis A. Chapado , Marta Alonso-Bernáldez , Andrea del Saz-Lara , Judit Gil-Zamorano , Emma Burgos-Ramos , María Rodríguez-Pérez , Diego Gómez-Coronado , Alberto Dávalos
{"title":"Dietary plant microRNAs as potential regulators of cellular cholesterol efflux","authors":"María del Carmen López de las Hazas , Joao Tomé-Carneiro , Livia Balaguer , Gema de la Peña , Luis A. Chapado , Marta Alonso-Bernáldez , Andrea del Saz-Lara , Judit Gil-Zamorano , Emma Burgos-Ramos , María Rodríguez-Pérez , Diego Gómez-Coronado , Alberto Dávalos","doi":"10.1016/j.arteri.2024.02.004","DOIUrl":"10.1016/j.arteri.2024.02.004","url":null,"abstract":"<div><h3>Aim</h3><div>Epidemiological evidence suggests adherence to vegetable-rich diets is associated to atheroprotective effects and bioactive components are most likely to play a relevant role. The notion of inter-kingdom regulation has opened a new research paradigm and perhaps microRNAs (miRNAs) from edible vegetables could influence consumer gene expression and lead to biological effects. We aimed to investigate the potential impact of broccoli-derived miRNAs on cellular cholesterol efflux in vitro.</div></div><div><h3>Methods</h3><div>Four miRNAs (miR159a, miR159b, miR166a and miR403) from <span><span>Brassica oleracea</span></span> var. <em>italica</em><span> (broccoli), a widely consumed cruciferous vegetable, were selected for further investigation, based on their high abundancy in this vegetable and their presence in other plants. Selected miRNAs were synthesized with a 3′-terminal 2′-O-methylation and their cellular toxicity, in vitro gastrointestinal resistance and cellular uptake were evaluated. Potential target genes within the mammalian transcriptome were assessed in silico following pathway analysis. In vitro cholesterol efflux was assessed in human THP-1-derived macrophages.</span></div></div><div><h3>Results</h3><div>miRNAs survival to in vitro GI digestion was around 1%, although some variation was seen between the four candidates. Cellular uptake by mammalian cells was confirmed, and an increase in cholesterol efflux was observed. Pathway analysis suggested these miRNAs are involved in biological processes related to phosphorylation, phosphatidylinositol and Wnt signaling, and to the insulin/IGF pathway.</div></div><div><h3>Conclusions</h3><div>Health-promoting properties attributed to cruciferous vegetables, might be mediated (at least in part) through miRNA-related mechanisms.</div></div>","PeriodicalId":45230,"journal":{"name":"Clinica e Investigacion en Arteriosclerosis","volume":"36 6","pages":"Pages 315-324"},"PeriodicalIF":1.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140872857","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":"A la familia del profesor Pedro Valdivielso Felices","authors":"","doi":"10.1016/j.arteri.2024.09.001","DOIUrl":"10.1016/j.arteri.2024.09.001","url":null,"abstract":"","PeriodicalId":45230,"journal":{"name":"Clinica e Investigacion en Arteriosclerosis","volume":"36 6","pages":"Pages 364-365"},"PeriodicalIF":1.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142663015","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}
Irene San Sebastián-Jaraba , María José Fernández-Gómez , Rafael Blázquez-Serra , Sandra Sanz-Andrea , Luis Miguel Blanco-Colio , Nerea Méndez-Barbero
{"title":"Modelo de cocultivo 3D in vitro de células endoteliales y vasculares de músculo liso humanas para el estudio del remodelado vascular patológico","authors":"Irene San Sebastián-Jaraba , María José Fernández-Gómez , Rafael Blázquez-Serra , Sandra Sanz-Andrea , Luis Miguel Blanco-Colio , Nerea Méndez-Barbero","doi":"10.1016/j.arteri.2024.03.007","DOIUrl":"10.1016/j.arteri.2024.03.007","url":null,"abstract":"<div><div>Pathological vascular remodeling of the vessel wall refers to the structural and functional changes of the vessel wall that occur in response to injury that eventually leads to cardiovascular disease. The vessel wall is composed of two main types of cells, endothelial cells and vascular smooth muscle cells, whose communication is crucial in both the development of the vasculature and the homeostasis of mature vessels. Changes in the dialogue between endothelial cells and vascular smooth muscle cells are associated with various pathological states that triggers remodeling of the vascular wall. For many years, considerable efforts have been made to develop effective diagnoses and treatments for these pathologies by studying their mechanisms in both <em>in vitro</em> and <em>in vivo</em> models. Compared to animal models, <em>in vitro</em> models can provide great opportunities to obtain data in a more homogeneous, economical and massive way, providing an overview of the signaling pathways responsible for these pathologies. The implementation of three-dimensional in vitro co-culture models for the study of other pathologies has been postulated as a potentially applicable methodology, which determines the importance of its application in studies of cardiovascular diseases. In this article we present a method for culturing human endothelial cells and vascular smooth muscle cells, grown under non-adherent conditions, that generate three-dimensional spheroidal structures with greater physiological equivalence to <em>in vivo</em> conditions. This in vitro modeling could be used as a study tool to identify cellular and molecular mechanisms involved in the pathological processes underlying vascular remodeling.</div></div>","PeriodicalId":45230,"journal":{"name":"Clinica e Investigacion en Arteriosclerosis","volume":"36 6","pages":"Pages 356-363"},"PeriodicalIF":1.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140898853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Goren Saenz-Pipaon , Ana Cenarro , Jon Zazpe , Miriam Goñi-Oloriz , Esther Martinez-Aguilar , Florencio J.D. Machado , Francesco P. Marchese , Josune Orbe , Natalia López-Andrés , Fernando Civeira , Jose A. Paramo , David Lara-Astiaso , Carmen Roncal
{"title":"Novel protocol for the transcriptomic analysis of endothelial extracellular vesicles in atherosclerosis","authors":"Goren Saenz-Pipaon , Ana Cenarro , Jon Zazpe , Miriam Goñi-Oloriz , Esther Martinez-Aguilar , Florencio J.D. Machado , Francesco P. Marchese , Josune Orbe , Natalia López-Andrés , Fernando Civeira , Jose A. Paramo , David Lara-Astiaso , Carmen Roncal","doi":"10.1016/j.arteri.2024.08.003","DOIUrl":"10.1016/j.arteri.2024.08.003","url":null,"abstract":"<div><h3>Introduction</h3><div>Despite the key role of the endothelium in atherosclerosis, there are no direct techniques for its analysis. The study of extracellular vesicles of endothelial origin (EEVs), might lead to the identification of molecular signatures and early biomarkers of atherosclerosis. The aim of this work was to set up the methods for EEVs separation and transcriptomic analysis.</div></div><div><h3>Methods</h3><div>We adapted an antibody-magnetic-bead based immunocapture protocol for plasma EEVs separation from control (G1), subclinical atherosclerosis (G2) and peripheral artery disease subjects (PAD) (G3), and modified an ultra-low input RNASeq method (<em>n</em> <!-->=<!--> <!-->5/group). By bioinformatics analysis we compared the transcriptome of plasma EEVs with that of human aortic endothelial cells (TeloHAECs), and then, searched for differentially expressed genes (DEG) among EEVs of G1, G2 and G3. From those DEG, <em>UCP2</em> was selected for further validation in plasma EVs (qPCR), and <em>in vitro</em>, in stimulated TeloHAECs (IL-1β, TNFα, oxLDL and hypoxia).</div></div><div><h3>Results</h3><div>The RNASeq analysis of plasma EEVs rendered 1667 genes enriched in transcripts expressed by TeloHAECs (NES: 1.93, <em>p</em> adjust<!--> <!-->=<!--> <!-->1.4<sup>e−73</sup>). One hundred seventy DEGs were identified between G2 vs G1, and 180 between G3 vs G1, of which 17 were similarly expressed in G2 and G3 vs control, including <em>UCP2</em>. IL-1β and TNFα (10<!--> <!-->ng/mL, <em>p</em> <!--><<!--> <!-->0.05), hypoxia (1% O<sub>2</sub>, <em>p</em> <!-->=<!--> <!-->0.05) and oxLDL (100<!--> <!-->μg/mL, <em>p</em> <!-->=<!--> <!-->0.055) reduced <em>UCP2</em> expression in TeloHAECs.</div></div><div><h3>Conclusions</h3><div>We set up a protocol for EEVs separation and sequencing that might be useful for the identification of early markers of endothelial dysfunction in atherosclerosis.</div></div>","PeriodicalId":45230,"journal":{"name":"Clinica e Investigacion en Arteriosclerosis","volume":"36 6","pages":"Pages 343-355"},"PeriodicalIF":1.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142298094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Una nueva perspectiva sobre el papel regulador de los miRNAS. Regulación entre reinos","authors":"José Luis Sánchez-Quesada","doi":"10.1016/j.arteri.2024.10.003","DOIUrl":"10.1016/j.arteri.2024.10.003","url":null,"abstract":"","PeriodicalId":45230,"journal":{"name":"Clinica e Investigacion en Arteriosclerosis","volume":"36 6","pages":"Pages 341-342"},"PeriodicalIF":1.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142629139","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}