PDF(Pubmed)
Abstract：
Atherosclerosis is a complex condition that involves the accumulation of lipids and subsequent plaque formation in the arterial intima. There are various stimuli, cellular receptors, and pathways involved in this process, but oxidative modifications of low-density lipoprotein (ox-LDL) are particularly important in the onset and progression of atherosclerosis. Ox-LDLs promote foam-cell formation, activate proinflammatory pathways, and induce smooth-muscle-cell migration, apoptosis, and cell death. One of the major receptors for ox-LDL is LOX-1, which is upregulated in several cardiovascular diseases, including atherosclerosis. LOX-1 activation in endothelial cells promotes endothelial dysfunction and induces pro-atherogenic signaling, leading to plaque formation. The binding of ox-LDLs to LOX-1 increases the generation of reactive oxygen species (ROS), which can induce LOX-1 expression and oxidize LDLs, contributing to ox-LDL generation and further upregulating LOX-1 expression. This creates a vicious circle that is amplified in pathological conditions characterized by high plasma levels of LDLs. Although LOX-1 has harmful effects, the clinical significance of inhibiting this protein remains unclear. Further studies both in vitro and in vivo are needed to determine whether LOX-1 inhibition could be a potential therapeutic target to counteract the atherosclerotic process.
摘要：
动脉粥样硬化是一种复杂的疾病，涉及脂质的积累和随后在动脉内膜中的斑块形成。有各种各样的刺激，细胞受体，以及参与这个过程的途径，但低密度脂蛋白(ox-LDL)的氧化修饰在动脉粥样硬化的发生和进展中尤为重要.Ox-LDLs促进泡沫细胞的形成，激活促炎途径，并诱导平滑肌细胞迁移，凋亡，细胞死亡。ox-LDL的主要受体之一是LOX-1，它在几种心血管疾病中上调，包括动脉粥样硬化.内皮细胞中的LOX-1激活促进内皮功能障碍并诱导促动脉粥样硬化信号,导致斑块形成。ox-LDLs与LOX-1的结合增加了活性氧（ROS）的产生，可以诱导LOX-1表达并氧化LDLs，有助于ox-LDL生成并进一步上调LOX-1表达。这产生了恶性循环,其在以高血浆水平的LDLs为特征的病理状况中被放大。虽然LOX-1有有害影响，抑制该蛋白的临床意义尚不清楚.需要进一步的体外和体内研究以确定L0X-1抑制是否可能是潜在的治疗靶标以抵消动脉粥样硬化过程。
