Clinica e Investigacion en Arteriosclerosis最新文献

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Dietary plant microRNAs as potential regulators of cellular cholesterol efflux 作为细胞胆固醇外流潜在调节剂的膳食植物微RNA。
IF 1.9
Clinica e Investigacion en Arteriosclerosis Pub Date : 2024-11-01 DOI: 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
{"title":"Dietary plant microRNAs as potential regulators of cellular cholesterol efflux","authors":"María del Carmen López de las Hazas ,&nbsp;Joao Tomé-Carneiro ,&nbsp;Livia Balaguer ,&nbsp;Gema de la Peña ,&nbsp;Luis A. Chapado ,&nbsp;Marta Alonso-Bernáldez ,&nbsp;Andrea del Saz-Lara ,&nbsp;Judit Gil-Zamorano ,&nbsp;Emma Burgos-Ramos ,&nbsp;María Rodríguez-Pérez ,&nbsp;Diego Gómez-Coronado ,&nbsp;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}
引用次数: 0
A la familia del profesor Pedro Valdivielso Felices 致佩德罗-巴尔迪维尔索-费利克斯教授的家人
IF 1.9
Clinica e Investigacion en Arteriosclerosis Pub Date : 2024-11-01 DOI: 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}
引用次数: 0
Modelo de cocultivo 3D in vitro de células endoteliales y vasculares de músculo liso humanas para el estudio del remodelado vascular patológico 体外三维人内皮细胞和平滑肌细胞共培养模型,用于研究病理性血管重塑。
IF 1.9
Clinica e Investigacion en Arteriosclerosis Pub Date : 2024-11-01 DOI: 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
{"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 ,&nbsp;María José Fernández-Gómez ,&nbsp;Rafael Blázquez-Serra ,&nbsp;Sandra Sanz-Andrea ,&nbsp;Luis Miguel Blanco-Colio ,&nbsp;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}
引用次数: 0
Novel protocol for the transcriptomic analysis of endothelial extracellular vesicles in atherosclerosis 动脉粥样硬化中内皮细胞外囊泡转录组分析的新方案。
IF 1.9
Clinica e Investigacion en Arteriosclerosis Pub Date : 2024-11-01 DOI: 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
{"title":"Novel protocol for the transcriptomic analysis of endothelial extracellular vesicles in atherosclerosis","authors":"Goren Saenz-Pipaon ,&nbsp;Ana Cenarro ,&nbsp;Jon Zazpe ,&nbsp;Miriam Goñi-Oloriz ,&nbsp;Esther Martinez-Aguilar ,&nbsp;Florencio J.D. Machado ,&nbsp;Francesco P. Marchese ,&nbsp;Josune Orbe ,&nbsp;Natalia López-Andrés ,&nbsp;Fernando Civeira ,&nbsp;Jose A. Paramo ,&nbsp;David Lara-Astiaso ,&nbsp;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> <!-->&lt;<!--> <!-->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}
引用次数: 0
Una nueva perspectiva sobre el papel regulador de los miRNAS. Regulación entre reinos miRNAS 调控作用的新视角。跨领域调控。
IF 1.9
Clinica e Investigacion en Arteriosclerosis Pub Date : 2024-11-01 DOI: 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}
引用次数: 0
Identification of new therapeutic targets related to endoplasmic reticulum stress and mitochondrial dysfunction to reduce the risk of rupture in degenerative ascending aortic aneurysm. 确定与内质网应激和线粒体功能障碍有关的新治疗靶点,以降低退行性升主动脉瘤破裂的风险。
IF 1.9
Clinica e Investigacion en Arteriosclerosis Pub Date : 2024-10-17 DOI: 10.1016/j.arteri.2024.09.002
Rafael Almendra-Pegueros, Antonio J Barros-Membrilla, Elvira Pérez-Marlasca, Josep Julve, José Martinez-González, Cristina Rodriguez, María Galán
{"title":"Identification of new therapeutic targets related to endoplasmic reticulum stress and mitochondrial dysfunction to reduce the risk of rupture in degenerative ascending aortic aneurysm.","authors":"Rafael Almendra-Pegueros, Antonio J Barros-Membrilla, Elvira Pérez-Marlasca, Josep Julve, José Martinez-González, Cristina Rodriguez, María Galán","doi":"10.1016/j.arteri.2024.09.002","DOIUrl":"https://doi.org/10.1016/j.arteri.2024.09.002","url":null,"abstract":"<p><strong>Background: </strong>Ascending Thoracic Aortic Aneurysm (ATAA) is a progressive dilation of the aorta that can be complicated by its dissection leading to death in 80-90% of the patients. When associated with aging and atherosclerosis, the outcome is worse and reconstructive surgery is the only effective therapy. Our objective was to characterize differential expressed genes (DEG) involved in endoplasmic reticulum (ER) and mitochondria dysfunction in patients with degenerative ATAA.</p><p><strong>Methods: </strong>A transcriptomic analysis was performed by RNA sequencing using RNA isolated from ATAA of patients classified as degenerative (n=13) and multi-organ healthy donors (n=6). DEGs related to ER stress and mitochondrial dysfunction were identified with the DESeq2 package. Enriched pathway (Reactome) and protein interaction (PPI) analysis was performed with the clusterProfiles package. PPI of the selected DEGs was analyzed based on the string database and visualized by Cytoscape software.</p><p><strong>Results: </strong>Histology revealed a complete disorganization of the extracellular matrix (ECM) and cell loss in the aortic wall of ATAA patients where the upregulation of 15 DEGs and the downregulation of 13 DEGs that encode proteins related to ER stress (ATF4, EIF2AK3, HSPA5, ERN1, SEL1L), mitochondrial dysfunction (DNML1, IMMT, MT-CO3, MT-CYB, MT ND2, TIMM17B, MT-ERF1, TOMM5) and ECM was detected. The results of GO term and enriched pathway analysis indicated that these DEGs are mainly enriched in pathways related to aortic diseases.</p><p><strong>Conclusions: </strong>Our data show that proteins related to mitochondrial dysfunction and ER stress might be therapeutic targets for the treatment of ATAA.</p>","PeriodicalId":45230,"journal":{"name":"Clinica e Investigacion en Arteriosclerosis","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142477232","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}
引用次数: 0
The complexity of cardiovascular risk in women. Descriptive review. 女性心血管风险的复杂性。描述性综述。
IF 1.9
Clinica e Investigacion en Arteriosclerosis Pub Date : 2024-10-08 DOI: 10.1016/j.arteri.2024.08.005
J Ildefonzo Arocha Rodulfo, Gestne Aure Fariñez
{"title":"The complexity of cardiovascular risk in women. Descriptive review.","authors":"J Ildefonzo Arocha Rodulfo, Gestne Aure Fariñez","doi":"10.1016/j.arteri.2024.08.005","DOIUrl":"https://doi.org/10.1016/j.arteri.2024.08.005","url":null,"abstract":"<p><strong>Objectives: </strong>Cardiovascular diseases (CVD) are the greatest threat to the health of women and is the leading cause of death amongst women globally; however, cardiovascular disease in women remains understudied, under-recognized, underdiagnosed, and undertreated. The aim of this descriptive review is to summarize the existing problem and to identify the knowledge gaps in cardiovascular disease research, prevention, treatment, and access to care for women.</p><p><strong>Material and methods: </strong>This is a descriptive review of the literature based on numerous articles published in peer-reviewed journals since the beginning of this century related to the spectrum of cardiovascular disease in women.</p><p><strong>Results: </strong>There are several obstacles to improve cardiovascular disease outcomes in women. One of them is the lack of reliable, effective screening modalities since her participation in clinical trial is quite low. Other concern is the complexity of the female organism with several hormonal changes during her life and the hemodynamics stress during pregnancy. Moreover, in the last stage of their life several cardiometabolic risk factor may appear, most of them not recognized by the health team in primary care attention.</p><p><strong>Discussion: </strong>Effective strategies are required to address inequalities in the diagnosis, treatment and prevention of heart disease in women; to advance innovative solutions for early detection and oriented management; to clarify the underlying biological mechanisms that contribute to sex-specific differences in outcomes; and finally, reduce the global burden of cardiovascular disease in women.</p>","PeriodicalId":45230,"journal":{"name":"Clinica e Investigacion en Arteriosclerosis","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142394129","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}
引用次数: 0
Strategies to improve cardiovascular health and treatment of dyslipidemia in Spain. Expert Insights Project. 西班牙改善心血管健康和治疗血脂异常的策略。专家见解项目。
IF 1.9
Clinica e Investigacion en Arteriosclerosis Pub Date : 2024-09-19 DOI: 10.1016/j.arteri.2024.08.007
Juan Pedro-Botet, Román Freixa, Juan José Tamarit, José López-Miranda, Rosa Fernández-Olmo, Ovidio Muñiz-Grijalvo, Rafael Vázquez-García, Carlos Guijarro, Luis Rodríguez-Padial, José Luis Díaz-Díaz, Marisol Bravo-Amaro, José Luís Hernández, José Antonio Alarcón-Duque, José Alfredo Martin-Armas, Martín García-López, Juan Cosín-Sales
{"title":"Strategies to improve cardiovascular health and treatment of dyslipidemia in Spain. Expert Insights Project.","authors":"Juan Pedro-Botet, Román Freixa, Juan José Tamarit, José López-Miranda, Rosa Fernández-Olmo, Ovidio Muñiz-Grijalvo, Rafael Vázquez-García, Carlos Guijarro, Luis Rodríguez-Padial, José Luis Díaz-Díaz, Marisol Bravo-Amaro, José Luís Hernández, José Antonio Alarcón-Duque, José Alfredo Martin-Armas, Martín García-López, Juan Cosín-Sales","doi":"10.1016/j.arteri.2024.08.007","DOIUrl":"https://doi.org/10.1016/j.arteri.2024.08.007","url":null,"abstract":"<p><strong>Objectives: </strong>To gather opinions, recommendations, and proposals for improvement from Spanish clinicians on cardiovascular (CV) health, with particular focus on dyslipidemia management.</p><p><strong>Methods: </strong>The Expert Insights project involved 8face-to-face sessions held throughout Spain, attended by 138 CV health experts. Clinicians answered to 25 questions survey related to CV health and dyslipidemia control. Each session included an analysis and a discussion on the perceived realities and areas for improvement.</p><p><strong>Results: </strong>72% of centers have a standardized process for monitoring patients after a CV episode at discharge, but only 37% during their clinical follow-up. Patient care and management are dependent on the physician, with a lack of coordination between hospital specialties and primary care (PC). 95% of clinicians believe it is necessary to standarize treatment optimization. 65% of centers prescribe combined lipid-lowering treatment after a CV episode. Updating cLDL levels in the Therapeutic Positioning Report and standardizing and globalizing the prescription document would reduce iPCSK9 prescription barriers and lead to more equitable access.</p><p><strong>Conclusions: </strong>In Spain, there are significant deficiencies in the management of dyslipidemia, with a great need for a consensus on standardizing management processes and optimizing patient treatment. The opinions, recommendations, and improvement proposals from Spanish clinicians on CV health are an important starting point to improve the situation.</p>","PeriodicalId":45230,"journal":{"name":"Clinica e Investigacion en Arteriosclerosis","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142298095","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}
引用次数: 0
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 平滑肌细胞中赖氨酸氧化酶的表达决定了高胆固醇血症诱发的动脉粥样硬化的内膜钙化水平。
IF 1.9
Clinica e Investigacion en Arteriosclerosis Pub Date : 2024-09-01 DOI: 10.1016/j.arteri.2024.01.003
{"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}
引用次数: 0
Lipoproteína (a) es un factor predictor de no consecución de objetivos de C-LDL en pacientes con cardiopatía isquémica crónica 脂蛋白(a)是慢性心脏病患者无法达到低密度脂蛋白胆固醇目标的预测因素。
IF 1.9
Clinica e Investigacion en Arteriosclerosis Pub Date : 2024-09-01 DOI: 10.1016/j.arteri.2024.01.002
{"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)<!--> <!-->&gt;<!--> <!-->50<!--> <!-->mg/dL and Lp(a)<!--> <!-->≤<!--> <!-->50<!--> <!-->mg/dL. The association of Lp(a)<!--> <!-->&gt;<!--> <!-->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)<!--> <!-->&gt;<!--> <!-->50<!--> <!-->mg/dL was 30.8%. Patients with Lp(a)<!--> <!-->&gt;<!--> <!-->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)<!--> <!-->&gt;<!--> <!-->50<!--> <!-->mg/dL. Independent predictors of having elevated Lp(a) levels<!--> <!-->&gt;<!--> <!-->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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