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Severe hypertriglyceridemias: What is necessary and what is sufficient 严重高甘油三酯血症:什么是必要的,什么是足够的
Pub Date : 2024-12-01 Epub Date: 2025-02-04 DOI: 10.1016/j.artere.2025.100745
José Luis Díaz Díaz
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引用次数: 0
Familial chylomicronemia: New perspectives 家族性乳糜微粒血症:新观点
Pub Date : 2024-12-01 Epub Date: 2025-02-04 DOI: 10.1016/j.artere.2025.100747
Agustín Blanco Echevarría , María José Ariza Corbo , Ovidio Muñiz-Grijalvo , José Luis Díaz-Díaz
Familial chylomicronemia (FCS) is a very rare, underdiagnosed disorder that can cause abdominal pain and recurrent pancreatitis from childhood -potentially life-threatening- and chronic complications such as diabetes mellitus and exocrine pancreatic insufficiency. FCS affects the quality of life and mental health of those who suffer from it, aspects that must be taken into account in its treatment, based on a strict low-fat diet, which is difficult to adhere to and persist. People with FCS lack the lipolytic capacity to hydrolyze triglycerides (TG) and have a minimal or null response to conventional lipid-lowering treatments. ApoCIII antagonists, specifically volanesorsen, olezarsen and ARO-APOC3, are the most promising drugs to reduce TG concentrations in patients with FCS. Anti-ANGPTL3 therapies appear to be less effective. More clinical trials and new pharmacological treatments are needed to improve the quality of life and prognosis of people with FCS.
家族性乳糜小红细胞血症(FCS)是一种非常罕见的未被诊断的疾病,可引起腹痛和儿童期复发性胰腺炎-可能危及生命-以及慢性并发症,如糖尿病和外分泌胰腺功能不全。FCS影响患者的生活质量和心理健康,在治疗时必须考虑到这些方面,治疗的基础是严格的低脂饮食,这种饮食很难坚持和坚持。FCS患者缺乏水解甘油三酯(TG)的解脂能力,对常规降脂治疗反应极小或无效。ApoCIII拮抗剂,特别是volanesorsen, olezarsen和ARO-APOC3,是最有希望降低FCS患者TG浓度的药物。抗angptl3治疗似乎效果较差。需要更多的临床试验和新的药物治疗来改善FCS患者的生活质量和预后。
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引用次数: 0
Strict control of atherogenic cholesterol and cardiovascular disease prevention 严格控制致动脉粥样硬化胆固醇,预防心血管疾病
Pub Date : 2024-12-01 Epub Date: 2025-02-04 DOI: 10.1016/j.artere.2025.100744
Carlos Guijarro
The role of LDL cholesterol as a causal agent of arteriosclerosis is scientifically consolidated. A number of seminal clinical trials of the highest scientific quality (randomized, controlled, double-blind versus placebo) in the last 40 years have confirmed that lipid lowering therapy with progressively ambitious therapeutic goals is associated with reductions in cardiovascular complications in the absence of major side effects at least up to the range of 30 mg/dL of LDL cholesterol. Drugs that have demonstrated these effects act by reducing circulating LDL cholesterol by upregulating the LDL receptor, independently of their primary action: inhibition of synthesis (statins, bempedoic acid), or absorption of cholesterol (ezetimibe) and promoting recycling of the LDL receptor via PCSK9 blockade. The early reduction of LDL cholesterol and its maintenance over time reinforce the protective effect of these drugs. Additional efforts are needed to improve the LDL control of high-risk patients to reduce their cardiovascular complications.
低密度脂蛋白胆固醇作为动脉硬化诱因的作用在科学上得到了巩固。在过去的40年里,许多具有最高科学质量的开创性临床试验(随机、对照、双盲与安慰剂对照)已经证实,具有逐步雄心治疗目标的降脂治疗与心血管并发症的减少有关,至少在LDL胆固醇30 mg/dL范围内没有主要副作用。已经证明这些作用的药物通过提高LDL受体来降低循环中的LDL胆固醇,而独立于它们的主要作用:抑制合成(他汀类药物、苯甲醚酸)或胆固醇的吸收(依折替米贝),并通过PCSK9阻断促进LDL受体的再循环。低密度脂蛋白胆固醇的早期降低及其随时间的维持加强了这些药物的保护作用。需要进一步努力改善高危患者的LDL控制,以减少其心血管并发症。
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引用次数: 0
Risk factors and assessment of subclinical atherosclerosis in patients with psoriatic arthritis 银屑病关节炎患者亚临床动脉粥样硬化的风险因素和评估
Pub Date : 2024-11-01 Epub Date: 2024-11-22 DOI: 10.1016/j.artere.2024.11.002
Zhoulan Zheng , Qianru Liu , Zhenan Zhang , Qianyu Guo , Liyun Zhang , Gailian Zhang

Objective

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.
目的了解亚临床动脉粥样硬化(SCA)在银屑病关节炎(PsA)患者中的发病率;探讨PsA合并SCA与传统心血管危险因素和疾病活动之间的相关性;比较弗雷明汉风险评分(FRS)和动脉粥样硬化性心血管疾病(ASCVD)评分的作用。方法我们纳入了50名符合CASPAR分类标准的PsA患者、50名糖尿病患者和50名健康人。我们收集了所有患者的临床数据,评估了 PsA 患者的最小疾病活动度(MDA)、银屑病关节炎疾病活动度指数(DAPSA)、ASCVD 和 FRS,并测量了颈动脉内膜中层厚度。吸烟、饮酒、ASCVD、FRS 是 PsA 伴有 SCA 的风险因素(P < 0.05)。银屑病(PsO)病程、PtGA、VAS 和 DAPSA 是患有 SCA 的 PsA 的风险因素(P < 0.05)。结论与健康对照组相比,PsA 患者的 SCA 患病率更高。高DAPSA是PsA合并SCA的风险因素。颈动脉超声可监测PsA患者的SCA,改善心血管风险分层。
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引用次数: 0
Dietary plant microRNAs as potential regulators of cellular cholesterol efflux 膳食植物微RNA是细胞胆固醇外流的潜在调节因子
Pub Date : 2024-11-01 Epub Date: 2024-11-22 DOI: 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.
目的流行病学证据表明,坚持食用富含蔬菜的饮食与动脉粥样硬化的保护作用有关,而生物活性成分最有可能发挥相关作用。王国间调控的概念开辟了一个新的研究范式,食用蔬菜中的微 RNA(miRNA)可能会影响消费者的基因表达并导致生物效应。我们的目的是研究西兰花衍生的 miRNAs 对体外细胞胆固醇外流的潜在影响。方法根据西兰花这种广泛食用的十字花科蔬菜中的高丰度miRNAs及其在其他植物中的存在情况,我们从芸薹属欧芹(Brassica oleracea)变种(西兰花)中选取了四个miRNAs(miR159a、miR159b、miR166a和miR403)进行进一步研究。对所选的 miRNA 进行了 3′-末端 2′-O-甲基化合成,并评估了它们的细胞毒性、体外胃肠道耐受性和细胞吸收率。通过路径分析,对哺乳动物转录组中的潜在靶基因进行了硅评估。结果miRNAs的体外胃肠道消化存活率约为1%,但四种候选RNA之间存在一定差异。哺乳动物细胞的摄取得到证实,并观察到胆固醇外流增加。途径分析表明,这些 miRNAs 参与了磷酸化、磷脂酰肌醇和 Wnt 信号转导以及胰岛素/IGF 途径相关的生物过程。
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引用次数: 0
A new perspective on the regulatory role of miRNAS. Cross-kingdom regulation miRNAS 调控作用的新视角。跨领域调控
Pub Date : 2024-11-01 Epub Date: 2024-11-22 DOI: 10.1016/j.artere.2024.10.003
José Luis Sánchez-Quesada
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引用次数: 0
In vitro 3D co-culture model of human endothelial and smooth muscle cells to study pathological vascular remodeling 研究病理性血管重塑的人内皮细胞和平滑肌细胞体外三维共培养模型
Pub Date : 2024-11-01 Epub Date: 2024-11-13 DOI: 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.
血管壁的病理性血管重塑是指血管壁的结构和功能因损伤而发生变化,最终导致心血管疾病(CVD)。血管壁主要由两类细胞组成,即内皮细胞(EC)和血管平滑肌细胞(VSMC),它们之间的交流对血管的发育和成熟血管的平衡至关重要。血管内皮细胞和血管平滑肌细胞之间对话的变化与引发血管壁重塑的各种病理状态有关。多年来,人们一直致力于通过在体外和体内模型中研究这些病理机制来开发有效的诊断和治疗方法。与动物模型相比,体外模型能以更均匀、更经济、更大规模的方式获取数据,为了解导致这些病症的信号通路提供了绝佳机会。三维体外共培养模型被认为是研究其他病理的一种潜在适用方法,这决定了它在心血管疾病研究中应用的重要性。在这篇文章中,我们介绍了一种在非粘附条件下培养人内皮细胞和血管平滑肌细胞的方法,这种方法可生成三维球形结构,其生理特性与体内条件更为接近。这种体外建模可作为一种研究工具,用于确定血管重塑的病理过程所涉及的细胞和分子机制。
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引用次数: 0
Clinical characterization and detection of subclinical atherosclerosis in subjects with extreme hyperalphalipoproteinemia 极度高脂蛋白血症患者的临床特征和亚临床动脉粥样硬化检测
Pub Date : 2024-11-01 Epub Date: 2024-10-18 DOI: 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.
导言和目的高密度脂蛋白胆固醇(HDL-C)水平与心血管疾病死亡之间的关系呈 U 型,在极端情况下呈上升趋势。该研究的目的是了解极端高脑积水患者(HAE)的特征。材料和方法共招募了 53 例 HAE 患者,其中女性 24 例(HDL-C 为 135 毫克/分升),男性 29 例(HDL-C 为 116 毫克/分升)。研究人员详细询问了病史,并收集了关于地中海饮食习惯和体育锻炼情况的调查问卷。结果最常见的心血管风险因素(CVRF)是血脂异常(64%),与高血压(女性为 21%,男性为 55%,P = 0.01)和其他心血管风险因素(如糖尿病)不同,男女之间没有显著差异。7%的患者曾患心血管疾病,女性的低密度脂蛋白胆固醇(P = 0.002)和高密度脂蛋白胆固醇(HDL-C)高于男性(无明显差异)。53%的病例检测出斑块,男性发病率更高。有斑块的患者年龄较大,饮酒较多,吸烟较多(p < 0.05)。半数以上的患者存在亚临床动脉粥样硬化。年龄、饮酒和吸烟与斑块的存在有独立关联,但我们的数据并未显示高密度脂蛋白胆固醇水平的显著影响。
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引用次数: 0
To the family of professor Pedro Valdivielso Felices 致佩德罗-巴尔迪维尔索-费利克斯教授的家人
Pub Date : 2024-11-01 Epub Date: 2024-10-16 DOI: 10.1016/j.artere.2024.10.002
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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
Pub Date : 2024-11-01 Epub Date: 2024-11-22 DOI: 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.
导言尽管内皮在动脉粥样硬化中起着关键作用,但目前还没有直接分析内皮的技术。研究内皮细胞外囊泡(EEVs)可能会发现动脉粥样硬化的分子特征和早期生物标志物。这项工作的目的是建立 EEVs 分离和转录组分析的方法。方法我们采用了基于抗体-磁珠的免疫捕获方案,从对照组(G1)、亚临床动脉粥样硬化组(G2)和外周动脉疾病组(PAD)(G3)分离血浆 EEVs,并修改了超低输入 RNASeq 方法(n = 5/组)。通过生物信息学分析,我们比较了血浆EEV和人主动脉内皮细胞(TeloHAECs)的转录组,然后在G1、G2和G3的EEV中寻找差异表达基因(DEG)。结果对血浆 EEVs 进行 RNASeq 分析后,发现 TeloHAECs 表达的转录本中富集了 1667 个基因(NES:1.93,p adjust = 1.4e-73)。在 G2 与 G1 之间发现了 170 个 DEGs,在 G3 与 G1 之间发现了 180 个 DEGs,其中 17 个基因在 G2 和 G3 与对照组中表达相似,包括 UCP2。IL-1β和TNFα(10 ng/mL,p < 0.05)、缺氧(1% O2,p = 0.05)和oxLDL(100 μg/mL,p = 0.055)降低了UCP2在TeloHAECs中的表达。
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引用次数: 0
期刊
Clínica e Investigación en Arteriosclerosis (English Edition)
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