Thangasparan Sahsikala, Kamisah Yusof, Ugusman Azizah, Mohamad Anuar Nur Najmi, Ibrahim Nurul 'Izzah
Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Bandar Tun Razak, Cheras 56000, Kuala Lumpur, Malaysia.
Cardiovascular and Pulmonary Research Group, Universiti Kebangsaan Malaysia, Bangi 43600, Selangor, Malaysia.
Int J Mol Sci. 2024 Dec 11;25(24):13292. doi: 10.3390/ijms252413292.
Cardiovascular diseases (CVD) are the number one cause of death worldwide, with atherosclerosis, which is the formation of fatty plaques in the arteries, being the most common underlying cause. The activation of inflammatory events and endothelium dysfunction are crucial for the development and pathophysiology of atherosclerosis. Elevated circulating levels of low-density lipoprotein (LDL) have been associated with severity of atherosclerosis. LDL can undergo oxidative modifications, resulting in oxidised LDL (oxLDL). OxLDL has been found to have antigenic potential and contribute significantly to atherosclerosis-associated inflammation by activating innate and adaptive immunity. Various inflammatory stimuli such as interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-α) and intercellular adhesion molecule 1 (ICAM-1) play major roles in atherosclerosis. To date, studies have provided valuable insights into the role of oxLDL in the development of atherosclerosis. However, there remains a gap in understanding the specific pathways involved in this process. This review aims to provide and discuss the mechanisms by which oxLDL modulates signalling pathways that cause cardiovascular diseases by providing in vitro and in vivo experimental evidence. Its critical role in triggering and sustaining endothelial dysfunction highlights its potential as a therapeutic target. Advancing the understanding of its atherogenic role and associated signalling pathways could pave the way for novel targeted therapeutic strategies to combat atherosclerosis more effectively.
心血管疾病（CVD）是全球首要死因，动脉粥样硬化作为最常见的潜在病因，是指动脉中脂肪斑块的形成。炎症反应激活和内皮功能障碍对动脉粥样硬化的发展及病理生理学过程至关重要。循环中低密度脂蛋白（LDL）水平升高与动脉粥样硬化的严重程度相关。LDL可发生氧化修饰，形成氧化型LDL（oxLDL）。已发现oxLDL具有抗原性，并通过激活固有免疫和适应性免疫，对动脉粥样硬化相关炎症有显著促进作用。多种炎症刺激因子，如白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）和细胞间黏附分子1（ICAM-1）在动脉粥样硬化中起主要作用。迄今为止，研究已对oxLDL在动脉粥样硬化发展中的作用提供了有价值的见解。然而，在理解这一过程所涉及的具体途径方面仍存在差距。本综述旨在通过提供体外和体内实验证据，阐述并讨论oxLDL调节导致心血管疾病的信号通路的机制。其在引发和维持内皮功能障碍中的关键作用凸显了其作为治疗靶点的潜力。深入了解其致动脉粥样硬化作用及相关信号通路，可为更有效地对抗动脉粥样硬化的新型靶向治疗策略铺平道路。
