Center for Molecular Cardiology, University of Zurich, Wagistreet 12, Schlieren 8952, Switzerland.
Department of Molecular Pathophysiology, Shinshu University School of Medicine, Shinshu University 3-1-1, Asahi, Matsumoto 390-8621, Japan.
Eur Heart J. 2021 May 7;42(18):1797-1807. doi: 10.1093/eurheartj/ehaa770.
Cardiovascular diseases (CVDs), specifically lipid-driven atherosclerotic CVDs, remain the number one cause of death worldwide. The lectin-like oxidized low-density lipoprotein (LDL) receptor-1 (LOX-1), a scavenger receptor that promotes endothelial dysfunction by inducing pro-atherogenic signalling and plaque formation via the endothelial uptake of oxidized LDL (oxLDL) and electronegative LDL, contributes to the initiation, progression, and destabilization of atheromatous plaques, eventually leading to the development of myocardial infarction and certain forms of stroke. In addition to its expression in endothelial cells, LOX-1 is expressed in macrophages, cardiomyocytes, fibroblasts, dendritic cells, lymphocytes, and neutrophils, further implicating this receptor in multiple aspects of atherosclerotic plaque formation. LOX-1 holds promise as a novel diagnostic and therapeutic target for certain CVDs; therefore, understanding the molecular structure and function of LOX-1 is of critical importance. In this review, we highlight the latest scientific findings related to LOX-1, its ligands, and their roles in the broad spectrum of CVDs. We describe recent findings from basic research, delineate their translational value, and discuss the potential of LOX-1 as a novel target for the prevention, diagnosis, and treatment of related CVDs.
心血管疾病(CVDs),特别是脂质驱动的动脉粥样硬化性 CVDs,仍然是全球头号死因。凝集素样氧化低密度脂蛋白(LDL)受体-1(LOX-1)是一种清道夫受体,通过诱导促动脉粥样硬化信号和斑块形成,通过内皮摄取氧化 LDL(oxLDL)和带负电 LDL,促进内皮功能障碍,导致动脉粥样硬化斑块的起始、进展和不稳定,最终导致心肌梗死和某些类型的中风。除了在血管内皮细胞中表达外,LOX-1 还在巨噬细胞、心肌细胞、成纤维细胞、树突状细胞、淋巴细胞和中性粒细胞中表达,这进一步表明该受体参与了动脉粥样硬化斑块形成的多个方面。LOX-1 有望成为某些 CVDs 的新型诊断和治疗靶点;因此,了解 LOX-1 的分子结构和功能至关重要。在这篇综述中,我们重点介绍了与 LOX-1、其配体及其在广泛的 CVDs 中的作用相关的最新科学发现。我们描述了基础研究的最新发现,阐述了它们的转化价值,并讨论了 LOX-1 作为预防、诊断和治疗相关 CVDs 的新型靶点的潜力。