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使用动脉粥样硬化动物模型进行多组学研究的现状与挑战

Current status and challenges of multi-omics research using animal models of atherosclerosis.

作者信息

Mitić Tijana, Georgescu Adriana, Alexandru-Moise Nicoleta, Davies Michael J, Vindis Cecile, Novella Susana, Gerdts Eva, Kararigas Georgios, Wettinger Stephanie Bezzina, Formosa Melissa M, Kwak Brenda R, Molica Filippo, Amigo Nuria, Caporali Andrea, de la Cuesta Fernando, Hall Ignacio Fernando, Chroni Angeliki, Martelli Fabio, Schmid Johannes A, Magni Paolo, Kardassis Dimitris

机构信息

Centre for Cardiovascular Science (CVS), Queen's Medical Research Institute (QMRI), University of Edinburgh, Edinburgh BioQuarter, United Kingdom.

Department of Pathophysiology and Cellular Pharmacology, Institute of Cellular Biology and Pathology 'Nicolae Simionescu', Bucharest, Romania.

出版信息

J Mol Cell Cardiol Plus. 2025 Jul 10;13:100476. doi: 10.1016/j.jmccpl.2025.100476. eCollection 2025 Sep.

Abstract

Atherosclerosis is an underlying cause of cardiovascular diseases (CVD) which account for most deaths worldwide. Use of diverse preclinical models of atherosclerosis has been implemental in understanding the underlying mechanisms, the implicated cell types, the genes and the molecules at play in the onset and progression of atherosclerotic plaques. Although significant research advancements have been made, further research is necessary to delve into factors influencing plaque types, site preference within the vasculature, interactions with adjacent tissues (liver, pancreas and perivascular adipose tissue), inflammation and sex-based disparities, among others. The conventional low throughput methodologies which concentrate on individual cells, genes or metabolites are inadequate to tackle the complex and heterogeneous nature of atherosclerosis. With recent advancement in multi-omics and bioinformatics, research approaches have illuminated a clearer understanding of atherosclerosis. Consequently, these advancements pave the path to design novel therapeutics to complement currently approved lipid-lowering and other effective treatments. In this article, we summarize and critically evaluate the findings derived from recent high throughput single- or multi-omic studies conducted in animal models of atherosclerosis. We also delve into the challenges associated with using experimental animals to model human atherosclerosis and contemplate the essential enhancements needed to better mimic human conditions. We further discuss the requirement of establishing a structured multi-omic database for atherosclerosis research, enabling broader access and utilisation within the scientific community.

摘要

动脉粥样硬化是心血管疾病(CVD)的一个根本原因,而心血管疾病是全球大多数死亡的原因。使用多种动脉粥样硬化临床前模型有助于理解动脉粥样硬化斑块发生和发展的潜在机制、涉及的细胞类型、基因和分子。尽管已经取得了重大的研究进展,但仍有必要进一步研究影响斑块类型、血管系统内的部位偏好、与相邻组织(肝脏、胰腺和血管周围脂肪组织)的相互作用、炎症和基于性别的差异等因素。传统的专注于单个细胞、基因或代谢物的低通量方法不足以应对动脉粥样硬化的复杂性和异质性。随着多组学和生物信息学的最新进展,研究方法为动脉粥样硬化提供了更清晰的认识。因此,这些进展为设计新的治疗方法铺平了道路,以补充目前批准的降脂和其他有效治疗方法。在本文中,我们总结并批判性地评估了最近在动脉粥样硬化动物模型中进行的高通量单组学或多组学研究的结果。我们还深入探讨了使用实验动物模拟人类动脉粥样硬化所面临的挑战,并思考更好地模拟人类情况所需的必要改进。我们进一步讨论了建立一个结构化的动脉粥样硬化研究多组学数据库的必要性,以便在科学界更广泛地获取和利用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/702f/12301843/279884863778/gr1.jpg

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