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.artere.2024.11.002","DOIUrl":"10.1016/j.artere.2024.11.002","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":100263,"journal":{"name":"Clínica e Investigación en Arteriosclerosis (English Edition)","volume":"36 6","pages":"Pages 333-340"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142705853","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.artere.2024.10.003
José Luis Sánchez-Quesada
{"title":"A new perspective on the regulatory role of miRNAS. Cross-kingdom regulation","authors":"José Luis Sánchez-Quesada","doi":"10.1016/j.artere.2024.10.003","DOIUrl":"10.1016/j.artere.2024.10.003","url":null,"abstract":"","PeriodicalId":100263,"journal":{"name":"Clínica e Investigación en Arteriosclerosis (English Edition)","volume":"36 6","pages":"Pages 341-342"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142705851","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.artere.2024.11.001
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.artere.2024.11.001","DOIUrl":"10.1016/j.artere.2024.11.001","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 <em>Brassica oleracea</em> var. <em>italica</em> (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.</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":100263,"journal":{"name":"Clínica e Investigación en Arteriosclerosis (English Edition)","volume":"36 6","pages":"Pages 315-324"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142705850","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.artere.2024.11.004
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 (CVD). The vessel wall is composed of two main types of cells, endothelial cells (EC) and vascular smooth muscle cells (VSMC), whose communication is crucial in both the development of the vasculature and the homeostasis of mature vessels. Changes in the dialogue between ECs and VSMCs 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":"In vitro 3D co-culture model of human endothelial and smooth muscle cells to study pathological vascular remodeling","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.artere.2024.11.004","DOIUrl":"10.1016/j.artere.2024.11.004","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 (CVD). The vessel wall is composed of two main types of cells, endothelial cells (EC) and vascular smooth muscle cells (VSMC), whose communication is crucial in both the development of the vasculature and the homeostasis of mature vessels. Changes in the dialogue between ECs and VSMCs 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":100263,"journal":{"name":"Clínica e Investigación en Arteriosclerosis (English Edition)","volume":"36 6","pages":"Pages 356-363"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142705854","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.artere.2024.10.002
{"title":"To the family of professor Pedro Valdivielso Felices","authors":"","doi":"10.1016/j.artere.2024.10.002","DOIUrl":"10.1016/j.artere.2024.10.002","url":null,"abstract":"","PeriodicalId":100263,"journal":{"name":"Clínica e Investigación en Arteriosclerosis (English Edition)","volume":"36 6","pages":"Pages 364-365"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142705856","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.artere.2024.10.001
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 characterise 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":"Clinical characterization and detection of subclinical atherosclerosis in subjects with extreme hyperalphalipoproteinemia","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.artere.2024.10.001","DOIUrl":"10.1016/j.artere.2024.10.001","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 characterise 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":100263,"journal":{"name":"Clínica e Investigación en Arteriosclerosis (English Edition)","volume":"36 6","pages":"Pages 325-332"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142705852","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.artere.2024.11.003
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.artere.2024.11.003","DOIUrl":"10.1016/j.artere.2024.11.003","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":100263,"journal":{"name":"Clínica e Investigación en Arteriosclerosis (English Edition)","volume":"36 6","pages":"Pages 343-355"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142705855","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 : 2024-09-01DOI: 10.1016/j.artere.2024.09.001
Carme Ballester-Servera , Judith Alonso , Manel Taurón , Noemí Rotllán , Cristina Rodríguez , José Martínez-González
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/6 J) 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":"Lysyl oxidase expression in smooth muscle cells determines the level of intima calcification in hypercholesterolemia-induced atherosclerosis","authors":"Carme Ballester-Servera , Judith Alonso , Manel Taurón , Noemí Rotllán , Cristina Rodríguez , José Martínez-González","doi":"10.1016/j.artere.2024.09.001","DOIUrl":"10.1016/j.artere.2024.09.001","url":null,"abstract":"<div><h3>Introduction</h3><div>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.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>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/6 J) 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.</div></div><div><h3>Conclusions</h3><div>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.</div></div>","PeriodicalId":100263,"journal":{"name":"Clínica e Investigación en Arteriosclerosis (English Edition)","volume":"36 5","pages":"Pages 286-298"},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142418539","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.artere.2024.09.005
Teresa Arrobas-Velilla , María José Ariza , Miguel Ángel Rico-Corral , Pedro Valdivielso
Background
Teleconsultation in the context of clinical laboratories is a valuable tool for the early detection of dyslipidemia and prevention of cardiovascular risk. Here, we describe a patient who was referred to the Lipid Unit of the Virgen Macarena Hospital due to an alert for severe hypertriglyceridemia through its teleconsultation program.
Case presentation
A comprehensive clinical and biochemical study of the patient was carried out, and genetic testing was performed on the patient and his family. The proband and his family showed mild to severe hypertriglyceridemia and various secondary factors, together with a genetic background associated with a triglyceride-raising effect.
Conclusion
This extensive study has identified a family at high risk of cardiovascular disease and acute pancreatitis. These findings can help maximize lifestyle changes and improve the clinical management of their dyslipidemia.
{"title":"Early detection of severe hypertriglyceridemia using teleconsultation in a clinical laboratory setting","authors":"Teresa Arrobas-Velilla , María José Ariza , Miguel Ángel Rico-Corral , Pedro Valdivielso","doi":"10.1016/j.artere.2024.09.005","DOIUrl":"10.1016/j.artere.2024.09.005","url":null,"abstract":"<div><h3>Background</h3><div>Teleconsultation in the context of clinical laboratories is a valuable tool for the early detection of dyslipidemia and prevention of cardiovascular risk. Here, we describe a patient who was referred to the Lipid Unit of the Virgen Macarena Hospital due to an alert for severe hypertriglyceridemia through its teleconsultation program.</div></div><div><h3>Case presentation</h3><div>A comprehensive clinical and biochemical study of the patient was carried out, and genetic testing was performed on the patient and his family. The proband and his family showed mild to severe hypertriglyceridemia and various secondary factors, together with a genetic background associated with a triglyceride-raising effect.</div></div><div><h3>Conclusion</h3><div>This extensive study has identified a family at high risk of cardiovascular disease and acute pancreatitis. These findings can help maximize lifestyle changes and improve the clinical management of their dyslipidemia.</div></div>","PeriodicalId":100263,"journal":{"name":"Clínica e Investigación en Arteriosclerosis (English Edition)","volume":"36 5","pages":"Pages 299-302"},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142418540","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}
Imaging is instrumental in diagnosing and directing the management of atherosclerosis. In 1958 the first diagnostic coronary angiography (CA) was performed, and since then further development has led to new methods such as coronary CT angiography (CTA), optical coherence tomography (OCT), positron tomography (PET), and intravascular ultrasound (IVUS). Currently, CA remains powerful for visualizing coronary arteries; however, recent studies show the benefits of using other non-invasive techniques. This review identifies optimum imaging techniques for diagnosing and monitoring plaque stability. This becomes even direr now, given the rapidly rising incidence of atherosclerosis in society today. Many acute coronary events, including acute myocardial infarctions and sudden deaths, are attributable to plaque rupture. Although fatal, these events can be preventable. We discuss the factors affecting plaque integrity, such as increased inflammation, medications like statins, and increased lipid content. Some of these precipitating factors are identifiable through imaging. However, we also highlight significant complications arising in some modalities; in CA this can include ventricular arrhythmia and even death. Extending this, we elucidated from the literature that risk can also vary based on the location of arteries and their plaques. Promisingly, there are less invasive methods being trialled for assessing plaque stability, such as Cardiac Magnetic Resonance Imaging (CMR), which is already in use for other cardiac diseases like cardiomyopathies. Therefore, future research focusing on using imaging modalities in conjunction may be sensible, to bridge between the effectiveness of modalities, at the expense of increased complications, and vice versa.
成像技术在诊断和指导动脉粥样硬化的治疗方面发挥着重要作用。1958 年，第一例诊断性冠状动脉造影术（CA）问世，此后，冠状动脉 CT 血管造影术（CTA）、光学相干断层扫描（OCT）、正电子断层扫描（PET）和血管内超声波（IVUS）等新方法不断发展。目前，CA 仍是冠状动脉可视化的有力手段；但最近的研究表明，使用其他无创技术也有好处。本综述确定了诊断和监测斑块稳定性的最佳成像技术。鉴于当今社会动脉粥样硬化的发病率急剧上升，这一问题变得更加紧迫。许多急性冠状动脉事件，包括急性心肌梗死和猝死，都可归因于斑块破裂。虽然这些事件是致命的，但却是可以预防的。我们将讨论影响斑块完整性的因素，如炎症加剧、他汀类药物等药物以及脂质含量增加。其中一些诱发因素可以通过影像学识别。不过，我们也强调了某些模式下出现的重大并发症；在 CA 中，这可能包括室性心律失常甚至死亡。在此基础上，我们从文献中阐明，风险也会因动脉及其斑块的位置而异。令人欣慰的是，目前正在试用一些侵入性较小的方法来评估斑块的稳定性，如心脏磁共振成像（CMR），它已被用于其他心脏疾病，如心肌病。因此，未来的研究重点可能是结合使用成像模式，以增加并发症为代价在各种模式的有效性之间架起一座桥梁，反之亦然。
{"title":"Update on cardiac imaging: A critical analysis","authors":"Halia Shah , Samina Alim , Sonia Akther , Mahnoor Irfan , Jamolbi Rahmatova , Aneesa Arshad , Charlene Hui Ping Kok , Syeda Anum Zahra","doi":"10.1016/j.artere.2024.09.006","DOIUrl":"10.1016/j.artere.2024.09.006","url":null,"abstract":"<div><div>Imaging is instrumental in diagnosing and directing the management of atherosclerosis. In 1958 the first diagnostic coronary angiography (CA) was performed, and since then further development has led to new methods such as coronary CT angiography (CTA), optical coherence tomography (OCT), positron tomography (PET), and intravascular ultrasound (IVUS). Currently, CA remains powerful for visualizing coronary arteries; however, recent studies show the benefits of using other non-invasive techniques. This review identifies optimum imaging techniques for diagnosing and monitoring plaque stability. This becomes even direr now, given the rapidly rising incidence of atherosclerosis in society today. Many acute coronary events, including acute myocardial infarctions and sudden deaths, are attributable to plaque rupture. Although fatal, these events can be preventable. We discuss the factors affecting plaque integrity, such as increased inflammation, medications like statins, and increased lipid content. Some of these precipitating factors are identifiable through imaging. However, we also highlight significant complications arising in some modalities; in CA this can include ventricular arrhythmia and even death. Extending this, we elucidated from the literature that risk can also vary based on the location of arteries and their plaques. Promisingly, there are less invasive methods being trialled for assessing plaque stability, such as Cardiac Magnetic Resonance Imaging (CMR), which is already in use for other cardiac diseases like cardiomyopathies. Therefore, future research focusing on using imaging modalities in conjunction may be sensible, to bridge between the effectiveness of modalities, at the expense of increased complications, and vice versa.</div></div>","PeriodicalId":100263,"journal":{"name":"Clínica e Investigación en Arteriosclerosis (English Edition)","volume":"36 5","pages":"Pages 304-313"},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142418542","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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