Kardassis Dimitris, Vindis Cécile, Stancu Camelia Sorina, Toma Laura, Gafencu Anca Violeta, Georgescu Adriana, Alexandru-Moise Nicoleta, Molica Filippo, Kwak Brenda R, Burlacu Alexandrina, Hall Ignacio Fernando, Butoi Elena, Magni Paolo, Wu Junxi, Novella Susana, Gamon Luke F, Davies Michael J, Caporali Andrea, de la Cuesta Fernando, Mitić Tijana
University of Crete Medical School and Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology of Hellas, Heraklion, Greece.
CARDIOMET, Center for Clinical Investigation 1436 (CIC1436)/INSERM, Toulouse, France.
Vascul Pharmacol. 2025 Mar;158:107452. doi: 10.1016/j.vph.2024.107452. Epub 2024 Dec 10.
Despite the discovery and prevalent clinical use of potent lipid-lowering therapies, including statins and PCSK9 inhibitors, cardiovascular diseases (CVD) caused by atherosclerosis remain a large unmet clinical need, accounting for frequent deaths worldwide. The pathogenesis of atherosclerosis is a complex process underlying the presence of modifiable and non-modifiable risk factors affecting several cell types including endothelial cells (ECs), monocytes/macrophages, smooth muscle cells (SMCs) and T cells. Heterogeneous composition of the plaque and its morphology could lead to rupture or erosion causing thrombosis, even a sudden death. To decipher this complexity, various cell model systems have been developed. With recent advances in systems biology approaches and single or multi-omics methods researchers can elucidate specific cell types, molecules and signalling pathways contributing to certain stages of disease progression. Compared with animals, in vitro models are economical, easily adjusted for high-throughput work, offering mechanistic insights. Hereby, we review the latest work performed employing the cellular models of atherosclerosis to generate a variety of omics data. We summarize their outputs and the impact they had in the field. Challenges in the translatability of the omics data obtained from the cell models will be discussed along with future perspectives.
尽管已经发现并广泛临床应用了强效降脂疗法，包括他汀类药物和前蛋白转化酶枯草杆菌蛋白酶9（PCSK9）抑制剂，但动脉粥样硬化引起的心血管疾病（CVD）仍然是一个尚未得到充分满足的重大临床需求，在全球范围内导致频繁死亡。动脉粥样硬化的发病机制是一个复杂的过程，存在影响多种细胞类型（包括内皮细胞（ECs）、单核细胞/巨噬细胞、平滑肌细胞（SMCs）和T细胞）的可改变和不可改变的风险因素。斑块的异质性组成及其形态可能导致破裂或糜烂，从而引发血栓形成，甚至猝死。为了解开这种复杂性，已经开发了各种细胞模型系统。随着系统生物学方法以及单组学或多组学方法的最新进展，研究人员可以阐明促成疾病进展某些阶段的特定细胞类型、分子和信号通路。与动物相比，体外模型经济实惠，易于调整以进行高通量研究，能够提供机制方面的见解。在此，我们回顾了利用动脉粥样硬化细胞模型开展的最新研究工作，以生成各种组学数据。我们总结了这些研究的成果及其在该领域产生的影响。同时还将讨论从细胞模型获得的组学数据在可转化性方面面临的挑战以及未来展望。
