Pub Date : 2024-12-01DOI: 10.1016/j.arteri.2024.11.003
Ovidio Muñiz-Grijalvo , Agustín Blanco Echevarría , María José Ariza Corbo , José Luis Díaz-Díaz
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.
{"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}
Pub Date : 2024-11-01DOI: 10.1016/j.arteri.2024.03.005
Javier Espíldora-Hernández , Tania Díaz-Antonio , Jesús Olmedo-Llanes , Jesús Zarzuela León , José Rioja , Pedro Valdivielso , Miguel Ángel Sánchez-Chaparro , María José Ariza
Introduction and objectives
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).
Material and methods
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.
Results
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).
Conclusions
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.
{"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}
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.
Methods
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.
Results
The prevalence of SCA in PsA patients was significantly higher than that in healthy controls (44% vs 24%, P < 0.05). Smoking, drinking, ASCVD, FRS were the risk factors of PsA with SCA (P < 0.05). Psoriasis (PsO) duration, PtGA, VAS and DAPSA were the risk factors for PsA with SCA (P < 0.05). FRS and ASCVD scores underestimated SCA risk in PsA patients.
Conclusion
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.
{"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}
Pub Date : 2024-11-01DOI: 10.1016/j.arteri.2024.02.004
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
Aim
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.
Methods
Four miRNAs (miR159a, miR159b, miR166a and miR403) from Brassica oleracea var. italica (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.
Results
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.
Conclusions
Health-promoting properties attributed to cruciferous vegetables, might be mediated (at least in part) through miRNA-related mechanisms.
{"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}
Pub Date : 2024-11-01DOI: 10.1016/j.arteri.2024.09.001
{"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}
Pub Date : 2024-11-01DOI: 10.1016/j.arteri.2024.03.007
Irene San Sebastián-Jaraba , María José Fernández-Gómez , Rafael Blázquez-Serra , Sandra Sanz-Andrea , Luis Miguel Blanco-Colio , Nerea Méndez-Barbero
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 in vitro and in vivo models. Compared to animal models, in vitro 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 in vivo 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.
{"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}
Pub Date : 2024-11-01DOI: 10.1016/j.arteri.2024.08.003
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
Introduction
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.
Methods
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 (n = 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, UCP2 was selected for further validation in plasma EVs (qPCR), and in vitro, in stimulated TeloHAECs (IL-1β, TNFα, oxLDL and hypoxia).
Results
The RNASeq analysis of plasma EEVs rendered 1667 genes enriched in transcripts expressed by TeloHAECs (NES: 1.93, p adjust = 1.4e−73). 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 UCP2. IL-1β and TNFα (10 ng/mL, p < 0.05), hypoxia (1% O2, p = 0.05) and oxLDL (100 μg/mL, p = 0.055) reduced UCP2 expression in TeloHAECs.
Conclusions
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.
{"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}
Pub Date : 2024-11-01DOI: 10.1016/j.arteri.2024.10.003
José Luis Sánchez-Quesada
{"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}
Pub Date : 2024-09-01DOI: 10.1016/j.arteri.2024.01.003
Introduction
Cardiovascular calcification is an important public health issue with an unmeet therapeutic need. We had previously shown that lysyl oxidase (LOX) activity critically influences vascular wall smooth muscle cells (VSMCs) and valvular interstitial cells (VICs) calcification by affecting extracellular matrix remodeling. We have delved into the participation of LOX in atherosclerosis and vascular calcification, as well as in the mineralization of the aortic valve.
Methods
Immunohistochemical and expression studies were carried out in human atherosclerotic lesions and experimental models, valves from patients with aortic stenosis, VICs, and in a genetically modified mouse model that overexpresses LOX in CMLV (TgLOXCMLV). Hyperlipemia and atherosclerosis was induced in mice through the administration of adeno-associated viruses encoding a PCSK9 mutated form (AAV-PCSK9D374Y) combined with an atherogenic diet.
Results
LOX expression is increased in the neointimal layer of atherosclerotic lesions from human coronary arteries and in VSMC-rich regions of atheromas developed both in the brachiocephalic artery of control (C57BL/6J) animals transduced with PCSK9D374Y and in the aortic root of ApoE−/− mice. In TgLOXCMLV mice, PCSK9D374Y transduction did not significantly alter the enhanced aortic expression of genes involved in matrix remodeling, inflammation, oxidative stress and osteoblastic differentiation. Likewise, LOX transgenesis did not alter the size or lipid content of atherosclerotic lesions in the aortic arch, brachiocephalic artery and aortic root, but exacerbated calcification. Among lysyl oxidase isoenzymes, LOX is the most expressed member of this family in highly calcified human valves, colocalizing with RUNX2 in VICs. The lower calcium deposition and decreased RUNX2 levels triggered by the overexpression of the nuclear receptor NOR-1 in VICs was associated with a reduction in LOX.
Conclusions
Our results show that LOX expression is increased in atherosclerotic lesions, and that overexpression of this enzyme in VSMC does not affect the size of the atheroma or its lipid content, but it does affect its degree of calcification. Further, these data suggest that the decrease in calcification driven by NOR-1 in VICs would involve a reduction in LOX. These evidences support the interest of LOX as a therapeutic target in cardiovascular calcification.
{"title":"La expresión de la lisil oxidasa en las células musculares lisas determina el nivel de calcificación de la íntima en la aterosclerosis inducida por hipercolesterolemia","authors":"","doi":"10.1016/j.arteri.2024.01.003","DOIUrl":"10.1016/j.arteri.2024.01.003","url":null,"abstract":"<div><h3>Introduction</h3><p>Cardiovascular calcification is an important public health issue with an unmeet therapeutic need. We had previously shown that lysyl oxidase (LOX) activity critically influences vascular wall smooth muscle cells (VSMCs) and valvular interstitial cells (VICs) calcification by affecting extracellular matrix remodeling. We have delved into the participation of LOX in atherosclerosis and vascular calcification, as well as in the mineralization of the aortic valve.</p></div><div><h3>Methods</h3><p>Immunohistochemical and expression studies were carried out in human atherosclerotic lesions and experimental models, valves from patients with aortic stenosis, VICs, and in a genetically modified mouse model that overexpresses LOX in CMLV (TgLOX<sup>CMLV</sup>). Hyperlipemia and atherosclerosis was induced in mice through the administration of adeno-associated viruses encoding a PCSK9 mutated form (AAV-PCSK9<sup>D374Y</sup>) combined with an atherogenic diet.</p></div><div><h3>Results</h3><p>LOX expression is increased in the neointimal layer of atherosclerotic lesions from human coronary arteries and in VSMC-rich regions of atheromas developed both in the brachiocephalic artery of control (C57BL/6J) animals transduced with PCSK9<sup>D374Y</sup> and in the aortic root of ApoE<sup>−/−</sup> mice. In TgLOX<sup>CMLV</sup> mice, PCSK9<sup>D374Y</sup> transduction did not significantly alter the enhanced aortic expression of genes involved in matrix remodeling, inflammation, oxidative stress and osteoblastic differentiation. Likewise, LOX transgenesis did not alter the size or lipid content of atherosclerotic lesions in the aortic arch, brachiocephalic artery and aortic root, but exacerbated calcification. Among lysyl oxidase isoenzymes, LOX is the most expressed member of this family in highly calcified human valves, colocalizing with RUNX2 in VICs. The lower calcium deposition and decreased RUNX2 levels triggered by the overexpression of the nuclear receptor NOR-1 in VICs was associated with a reduction in LOX.</p></div><div><h3>Conclusions</h3><p>Our results show that LOX expression is increased in atherosclerotic lesions, and that overexpression of this enzyme in VSMC does not affect the size of the atheroma or its lipid content, but it does affect its degree of calcification. Further, these data suggest that the decrease in calcification driven by NOR-1 in VICs would involve a reduction in LOX. These evidences support the interest of LOX as a therapeutic target in cardiovascular calcification.</p></div>","PeriodicalId":45230,"journal":{"name":"Clinica e Investigacion en Arteriosclerosis","volume":"36 5","pages":"Pages 286-298"},"PeriodicalIF":1.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139944539","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}
Pub Date : 2024-09-01DOI: 10.1016/j.arteri.2024.01.002
Introduction and objectives
Lipoprotein (a) [Lp(a)] concentration influences serum low-density lipoprotein cholesterol (LDL-C) levels. How it influences the achievement of LDL-C targets established in the guidelines is not well studied. Our aim was to know the prevalence of elevated Lp(a) levels in patients with coronary artery disease, and to assess its influence on the achievement of LDL-C targets.
Method
We conducted a cross-sectional study in a cardiology department in Spain. A total of 870 patients with stable coronary artery disease had their lipid profile determined, including Lp(a). Patients were stratified into 2 groups according to Lp(a) > 50 mg/dL and Lp(a) ≤ 50 mg/dL. The association of Lp(a) > 50 mg/dL with achievement of LDL-C targets was assessed by logistic regression analysis.
Results
The prevalence of Lp(a) > 50 mg/dL was 30.8%. Patients with Lp(a) > 50 mg/dL had higher baseline (142.30 ± 47.54 vs. 130.47 ± 40.75 mg/dL; p = 0.0001) and current (72.91 ± 26.44 vs. 64.72 ± 25.30 mg/dL; p = 0.0001), despite the fact that they were treated with more high-potency statins (77.2 vs. 70.9%; p = 0.058) and more combination lipid-lowering therapy (37.7 vs. 25.7%; p = 0.001). The proportion of patients achieving target LDL-C was lower in those with Lp(a) > 50 mg/dL. Independent predictors of having elevated Lp(a) levels > 50 mg/dL were the use of high-potency statins (OR 1.5; 95% CI 1.08-2.14), combination lipid-lowering therapy with ezetimibe (OR 2.0; 95% CI 1.45-2.73) and failure to achieve a LDL-C ≤55 mg/dL (OR 2.3; 95% CI 1.63-3.23).
Conclusions
Elevated Lp(a) levels influence LDL-C levels and hinder the achievement of targets in patients at very high cardiovascular risk. New drugs that act directly on Lp(a) are needed in these patients.
引言和目的：脂蛋白 (a) [Lp(a)] 浓度会影响血清低密度脂蛋白胆固醇 (LDL-C) 水平。它如何影响实现指南中规定的低密度脂蛋白胆固醇目标尚未得到充分研究。我们的目的是了解冠心病患者脂蛋白（a）水平升高的发生率，并评估其对实现低密度脂蛋白胆固醇目标的影响：我们在西班牙的一家心脏病科进行了一项横断面研究。共有 870 名冠状动脉疾病稳定期患者接受了包括脂蛋白（a）在内的血脂测定。根据脂蛋白（a）>50 毫克/分升和脂蛋白（a）≤50 毫克/分升将患者分为两组。通过逻辑回归分析评估了脂蛋白（a）>50mg/dL与低密度脂蛋白胆固醇（LDL-C）达标率的关系：结果：脂蛋白（a）>50 毫克/分升的患病率为 30.8%。Lp(a)>50mg/dL 患者的基线（142.30±47.54 vs. 130.47±40.75mg/dL；p=0.0001）和当前（72.91±26.44 vs. 64.72±25.30mg/dL；p=0.0001）均较高，尽管他们接受了更多的高效他汀类药物治疗（77.2 vs. 70.9%；p=0.058）和更多的联合降脂治疗（37.7 vs. 25.7%；p=0.001）。Lp(a)>50mg/dL 的患者达到目标 LDL-C 的比例较低。使用高效他汀类药物（OR 1.5；95% CI 1.08-2.14）、使用依折麦布联合降脂治疗（OR 2.0；95% CI 1.45-2.73）和未能达到低密度脂蛋白胆固醇≤55mg/dL（OR 2.3；95% CI 1.63-3.23）是导致脂蛋白（a）水平升高>50mg/dL的独立预测因素：Lp（a）水平升高会影响低密度脂蛋白胆固醇水平，并阻碍心血管风险极高的患者达到目标。这些患者需要直接作用于脂蛋白（a）的新药。
{"title":"Lipoproteína (a) es un factor predictor de no consecución de objetivos de C-LDL en pacientes con cardiopatía isquémica crónica","authors":"","doi":"10.1016/j.arteri.2024.01.002","DOIUrl":"10.1016/j.arteri.2024.01.002","url":null,"abstract":"<div><h3>Introduction and objectives</h3><p>Lipoprotein (a) [Lp(a)] concentration influences serum low-density lipoprotein cholesterol (LDL-C) levels. How it influences the achievement of LDL-C targets established in the guidelines is not well studied. Our aim was to know the prevalence of elevated Lp(a) levels in patients with coronary artery disease, and to assess its influence on the achievement of LDL-C targets.</p></div><div><h3>Method</h3><p>We conducted a cross-sectional study in a cardiology department in Spain. A total of 870 patients with stable coronary artery disease had their lipid profile determined, including Lp(a). Patients were stratified into 2 groups according to Lp(a)<!--> <!-->><!--> <!-->50<!--> <!-->mg/dL and Lp(a)<!--> <!-->≤<!--> <!-->50<!--> <!-->mg/dL. The association of Lp(a)<!--> <!-->><!--> <!-->50<!--> <!-->mg/dL with achievement of LDL-C targets was assessed by logistic regression analysis.</p></div><div><h3>Results</h3><p>The prevalence of Lp(a)<!--> <!-->><!--> <!-->50<!--> <!-->mg/dL was 30.8%. Patients with Lp(a)<!--> <!-->><!--> <!-->50<!--> <!-->mg/dL had higher baseline (142.30<!--> <!-->±<!--> <!-->47.54 vs. 130.47<!--> <!-->±<!--> <!-->40.75<!--> <!-->mg/dL; p<!--> <!-->=<!--> <!-->0.0001) and current (72.91<!--> <!-->±<!--> <!-->26.44 vs. 64.72<!--> <!-->±<!--> <!-->25.30<!--> <!-->mg/dL; p<!--> <!-->=<!--> <!-->0.0001), despite the fact that they were treated with more high-potency statins (77.2 vs. 70.9%; p<!--> <!-->=<!--> <!-->0.058) and more combination lipid-lowering therapy (37.7 vs. 25.7%; p<!--> <!-->=<!--> <!-->0.001). The proportion of patients achieving target LDL-C was lower in those with Lp(a)<!--> <!-->><!--> <!-->50<!--> <!-->mg/dL. Independent predictors of having elevated Lp(a) levels<!--> <!-->><!--> <!-->50<!--> <!-->mg/dL were the use of high-potency statins (OR 1.5; 95% CI 1.08-2.14), combination lipid-lowering therapy with ezetimibe (OR 2.0; 95% CI 1.45-2.73) and failure to achieve a LDL-C ≤55<!--> <!-->mg/dL (OR 2.3; 95% CI 1.63-3.23).</p></div><div><h3>Conclusions</h3><p>Elevated Lp(a) levels influence LDL-C levels and hinder the achievement of targets in patients at very high cardiovascular risk. New drugs that act directly on Lp(a) are needed in these patients.</p></div>","PeriodicalId":45230,"journal":{"name":"Clinica e Investigacion en Arteriosclerosis","volume":"36 5","pages":"Pages 278-285"},"PeriodicalIF":1.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139944538","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}
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