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Statin-associated muscle symptoms: Not simply a genetic predisposition. 他汀类药物相关肌肉症状:不仅仅是遗传倾向
IF 4.9 2区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-11-09 DOI: 10.1016/j.atherosclerosis.2024.119047
Nicola Ferri, Alberto Corsini
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引用次数: 0
HDL and cardiovascular risk. 高密度脂蛋白与心血管风险
IF 4.9 2区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-11-09 DOI: 10.1016/j.atherosclerosis.2024.119050
Manuel Jesús Romero-Jiménez
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引用次数: 0
Extracellular peroxiredoxin 5 exacerbates atherosclerosis via the TLR4/MyD88 pathway 细胞外过氧化物酶 5 通过 TLR4/MyD88 途径加剧动脉粥样硬化
IF 4.9 2区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-11-09 DOI: 10.1016/j.atherosclerosis.2024.119052
Hyae Yon Kweon , Eun Ju Song , Se-Jin Jeong , SoonHo Lee , Seong-Keun Sonn , Seungwoon Seo , Jing Jin , Sinai Kim , Tae Kyeong Kim , Shin Hye Moon , Doyeon Kim , Young Mi Park , Hyun Ae Woo , Goo Taeg Oh

Backgroungd and aims

Peroxiredoxin 5 (PRDX5), an atypical 2-Cys peroxiredoxin (PRDX), is known to regulate global oxidative stresses and inflammatory responses. Inflammation and oxidative stress are pivotal factors in the development of atherosclerosis, especially in the context of vascular endothelial dysfunction. However, effects of PRDX5 on atherosclerosis remain unclear. This study aimed to elucidate the role of PRDX5 in the pathogenesis of atherosclerosis.

Methods

For in vivo analysis, normal chow diet 60-week old Apolipoprotein E knockout (ApoE−/−) and Prdx5−/−; ApoE−/− mice were used for the experiments. For in vitro analysis, human umbilical vein endothelial cells (HUVECs) were stimulated with oxidized LDL (oxLDL; 50 ng/ml) for 24hrs, following serum starvation by incubation with serum-free Endothelial Cell Growth Medium-2 (EGM-2) for 1hr.

Results

We observed elevated PRDX5 expression under atherosclerotic conditions in both humans and mice. Unexpectedly, Prdx5−/−; ApoE−/− mice exhibited reduced plaque formation, with no discernible difference in aortic hydrogen peroxide (H2O2) levels compared to ApoE−/− mice. Additionally, there was a notable decrease in macrophage accumulation and vascular inflammation in the atherosclerotic aorta of Prdx5−/−; ApoE−/−. In vitro, HUVECs stimulated with oxLDL showed upregulated PRDX5 expression in both lysate and culture medium. Moreover, PRDX5 knockdown in oxLDL-stimulated (oxLDL-siPRDX5) HUVECs significantly reduced the migration and adhesion of human monocytic cells (THP-1) to HUVECs, indicating diminished vascular immune responses. Mechanistically, both in vivo and in vitro, PRDX5 deficiency inhibited the Toll-like receptor 4 (TLR4)/Myeloid differentiation primary response 88 (MyD88) signaling pathway, resulting in reduced nuclear factor kappa B (NF-κB) and P38 phosphorylation. Furthermore, treatment with recombinant PRDX5 (rPRDX5) protein restored TLR4/MyD88 signaling in oxLDL-siPRDX5 HUVECs.

Conclusions

These data demonstrate that extracellular PRDX5 contributes to endothelial inflammation, promoting macrophage accumulation in the atherosclerotic aorta through activation of TLR4/MyD88/NF-κB and P38 signaling pathways, thereby exacerbating the progression of atherosclerosis.
背景和目的:众所周知,过氧化还原酶 5(PRDX5)是一种非典型的 2-Cys 过氧化还原酶(PRDX),可调节全球氧化应激和炎症反应。炎症和氧化应激是动脉粥样硬化发展的关键因素,尤其是在血管内皮功能障碍的情况下。然而,PRDX5 对动脉粥样硬化的影响仍不清楚。本研究旨在阐明 PRDX5 在动脉粥样硬化发病机制中的作用:体内分析:使用正常饲料喂养的 60 周龄载脂蛋白 E 基因敲除(ApoE-/-)小鼠和 Prdx5-/-; ApoE-/- 小鼠进行实验。为了进行体外分析,用氧化低密度脂蛋白(oxLDL;50 ng/ml)刺激人脐静脉内皮细胞(HUVECs)24 小时,然后用无血清的内皮细胞生长培养基-2(EGM-2)孵育 1 小时:结果:我们观察到,在动脉粥样硬化条件下,人和小鼠的 PRDX5 表达均升高。出乎意料的是,Prdx5-/-;载脂蛋白E-/-小鼠斑块形成减少,主动脉过氧化氢(H2O2)水平与载脂蛋白E-/-小鼠相比没有明显差异。此外,Prdx5-/-; ApoE-/-小鼠动脉粥样硬化主动脉中的巨噬细胞聚集和血管炎症也明显减少。在体外,受 oxLDL 刺激的 HUVEC 在裂解物和培养液中都显示出 PRDX5 表达上调。此外,在受 oxLDL 刺激的 HUVECs(oxLDL-siPRDX5)中敲除 PRDX5 能显著减少人单核细胞(THP-1)向 HUVECs 的迁移和粘附,这表明血管免疫反应减弱。从机制上讲,无论是在体内还是体外,PRDX5 的缺乏都抑制了 Toll 样受体 4(TLR4)/髓系分化初级反应 88(MyD88)信号通路,导致核因子卡巴 B(NF-κB)和 P38 磷酸化减少。此外,用重组 PRDX5(rPRDX5)蛋白处理可恢复 oxLDL-siPRDX5 HUVECs 中的 TLR4/MyD88 信号传导:这些数据表明,细胞外 PRDX5 有助于内皮炎症,通过激活 TLR4/MyD88/NF-κB 和 P38 信号通路促进巨噬细胞在动脉粥样硬化主动脉中的聚集,从而加剧动脉粥样硬化的进展。
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引用次数: 0
Unveiling feature importance biases in linear regression: Implications for protein-centric cardiovascular research. 揭示线性回归中的特征重要性偏差:以蛋白质为中心的心血管研究的意义。
IF 4.9 2区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-11-08 DOI: 10.1016/j.atherosclerosis.2024.119049
Yoshiyasu Takefuji
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引用次数: 0
Reply to: “Correspondence on: “Subclinical atherosclerosis: More data – More insights into prevention” ” 答复关于 "亚临床动脉粥样硬化"亚临床动脉粥样硬化:更多数据 - 更多预防见解" "
IF 4.9 2区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-11-06 DOI: 10.1016/j.atherosclerosis.2024.118634
Heinz Drexel, Andreas Festa
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引用次数: 0
PCSK9 inhibitors in the management of atherosclerotic cardiovascular disease: Current clinical trials and future directions PCSK9 抑制剂在动脉粥样硬化性心血管疾病治疗中的应用:当前的临床试验和未来方向。
IF 4.9 2区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-11-02 DOI: 10.1016/j.atherosclerosis.2024.119043
Wenyi Nie , Yingbin Yue , Jingqing Hu
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引用次数: 0
Nucleic acid liquid biopsies in cardiovascular disease: Cell-free RNA liquid biopsies in cardiovascular disease 心血管疾病中的核酸液体活检:心血管疾病中的无细胞 RNA 液体活检。
IF 4.9 2区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-11-01 DOI: 10.1016/j.atherosclerosis.2024.118584
Smriti Sharma , Tyler Artner , Klaus T. Preissner , Irene M. Lang
Cardiovascular diseases (CVD) and their complications continue to be the leading cause of mortality globally. With recent advancements in molecular analytics, individualized treatments are gradually applied to the diagnosis and treatment of CVD. In the field of diagnostics, liquid biopsy combined with modern analytical technologies is the most popular natural source to identify disease biomarkers, as has been successfully demonstrated in the cancer field. While it is not easy to obtain any diseased tissue for different types of CVD such as atherosclerosis, deep vein thrombosis or stroke, liquid biopsies provide a simple and non-invasive alternative to surgical tissue specimens to obtain dynamic molecular information reflecting disease states. The release of cell-free ribonucleic acids (cfRNA) from stressed/damaged/dying and/or necrotic cells is a common physiological phenomenon. CfRNAs are a heterogeneous population of various types of extracellular RNA found in body fluids (blood, urine, saliva, cerebrospinal fluid) or in association with vascular/atherosclerotic tissue, offering insights into disease pathology on a diagnostic front. In particular, cf-ribosomal RNA has been shown to act as a damaging molecule in several cardio-vascular disease conditions. Moreover, such pathophysiological functions of cfRNA in CVD have been successfully antagonized by the administration of RNases. In this review, we discuss the origin, structure, types, and potential utilization of cfRNA in the diagnosis of CVD. Together with the analysis of established CVD biomarkers, the profiling of cfRNA in body fluids may thereby provide a promising approach for early disease detection and monitoring.
心血管疾病(CVD)及其并发症仍然是全球死亡的主要原因。随着分子分析技术的不断进步,个体化治疗逐渐应用于心血管疾病的诊断和治疗。在诊断领域,液体活检与现代分析技术相结合,是确定疾病生物标志物最常用的天然来源,这一点已在癌症领域得到成功验证。虽然获取动脉粥样硬化、深静脉血栓或中风等不同类型心血管疾病的病变组织并不容易,但液体活检为获取反映疾病状态的动态分子信息提供了一种简单、无创的替代手术组织标本的方法。受压/受损/萎缩和/或坏死细胞释放出细胞游离核糖核酸(cfRNA)是一种常见的生理现象。CfRNA 是体液(血液、尿液、唾液、脑脊液)中或与血管/动脉粥样硬化组织相关的各种细胞外 RNA 的异质群,可提供诊断方面的疾病病理信息。特别是,cf-核糖体 RNA 已被证明在几种心血管疾病中起着破坏分子的作用。此外,cfRNA 在心血管疾病中的这些病理生理功能已被 RNase 成功拮抗。在这篇综述中,我们将讨论 cfRNA 的起源、结构、类型以及在心血管疾病诊断中的潜在用途。结合对已确定的心血管疾病生物标志物的分析,体液中的 cfRNA 分析可能会为疾病的早期检测和监测提供一种前景广阔的方法。
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引用次数: 0
Coronary artery calcium density progression: Should we measure it? 冠状动脉钙密度进展:我们应该测量它吗?
IF 4.9 2区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-11-01 DOI: 10.1016/j.atherosclerosis.2024.118618
Alexander C. Razavi, Roger S. Blumenthal, Mouaz H. Al-Mallah, Mahmoud Al Rifai
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引用次数: 0
Using artificial intelligence to study atherosclerosis from computed tomography imaging: A state-of-the-art review of the current literature 利用人工智能研究计算机断层扫描成像中的动脉粥样硬化:最新文献综述
IF 4.9 2区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-11-01 DOI: 10.1016/j.atherosclerosis.2024.117580
Laura Valentina Klüner, Kenneth Chan, Charalambos Antoniades
With the enormous progress in the field of cardiovascular imaging in recent years, computed tomography (CT) has become readily available to phenotype atherosclerotic coronary artery disease. New analytical methods using artificial intelligence (AI) enable the analysis of complex phenotypic information of atherosclerotic plaques. In particular, deep learning-based approaches using convolutional neural networks (CNNs) facilitate tasks such as lesion detection, segmentation, and classification. New radiotranscriptomic techniques even capture underlying bio-histochemical processes through higher-order structural analysis of voxels on CT images. In the near future, the international large-scale Oxford Risk Factors And Non-invasive Imaging (ORFAN) study will provide a powerful platform for testing and validating prognostic AI-based models. The goal is the transition of these new approaches from research settings into a clinical workflow.
In this review, we present an overview of existing AI-based techniques with focus on imaging biomarkers to determine the degree of coronary inflammation, coronary plaques, and the associated risk. Further, current limitations using AI-based approaches as well as the priorities to address these challenges will be discussed. This will pave the way for an AI-enabled risk assessment tool to detect vulnerable atherosclerotic plaques and to guide treatment strategies for patients.
近年来,随着心血管成像领域的巨大进步,计算机断层扫描(CT)已可随时用于冠状动脉粥样硬化疾病的表型分析。利用人工智能(AI)的新分析方法可以分析动脉粥样硬化斑块的复杂表型信息。特别是基于深度学习的卷积神经网络(CNN)方法,有助于完成病变检测、分割和分类等任务。新的放射转录组学技术甚至可以通过对 CT 图像上的体素进行高阶结构分析来捕捉潜在的生物组化过程。在不久的将来,国际大型牛津风险因素和无创成像(ORFAN)研究将为测试和验证基于人工智能的预后模型提供一个强大的平台。在这篇综述中,我们概述了现有的基于人工智能的技术,重点是确定冠状动脉炎症程度、冠状动脉斑块和相关风险的成像生物标志物。此外,我们还将讨论基于人工智能的方法目前存在的局限性以及应对这些挑战的优先事项。这将为人工智能风险评估工具检测易损动脉粥样硬化斑块和指导患者治疗策略铺平道路。
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引用次数: 0
Modeling human atherosclerotic lesions in the test tube: Are we there yet? 在试管中模拟人类动脉粥样硬化病变:我们成功了吗?
IF 4.9 2区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-11-01 DOI: 10.1016/j.atherosclerosis.2024.118560
Mary Gonzalez Melo, Arnold von Eckardstein, Jerome Robert
Atherosclerotic cardiovascular diseases remain a leading cause of morbidity and mortality worldwide. Atherogenesis is a slow and life-long process characterized by the accumulation of lipoproteins and immune cells within the arterial wall. Atherosclerosis has been successfully modeled in animals: However, there are economic, ethical, and translational concerns when using these models. There is also growing recognition of the need for robust human-based in vitro systems that can faithfully recapitulate key aspects of human atherosclerosis. Such systems may offer advantages in terms of scalability, reproducibility, and ability to manipulate specific variables, thereby facilitating a deeper understanding of disease mechanisms and accelerating the development of targeted therapeutics. Leveraging innovative in vitro platforms holds promise in complementing traditional animal models of atherosclerosis. In the present review, we discuss the advantages and disadvantages of recently developed models of atherosclerosis and propose ideas to be considered when developing future generations of models.
动脉粥样硬化性心血管疾病仍然是全球发病率和死亡率的主要原因。动脉粥样硬化的发生是一个缓慢而漫长的过程,其特点是脂蛋白和免疫细胞在动脉壁上的积聚。动脉粥样硬化已成功地在动物身上建模:然而,在使用这些模型时存在经济、伦理和转化方面的问题。越来越多的人认识到,需要能忠实再现人类动脉粥样硬化关键方面的稳健的人基体外系统。这类系统在可扩展性、可重复性和操纵特定变量的能力方面具有优势,从而有助于加深对疾病机制的理解,加快靶向治疗药物的开发。利用创新的体外平台有望补充传统的动脉粥样硬化动物模型。在本综述中,我们讨论了最近开发的动脉粥样硬化模型的优缺点,并提出了在开发下一代模型时应考虑的想法。
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引用次数: 0
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Atherosclerosis
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