Roles of Ox-LDL in atherosclerosis
| Role | Description |
|---|---|
| Induction of endothelial cell dysfunction | Ox-LDL binds to its receptor, LOX-1, on endothelial cells, leading to a decrease in nitric oxide production, which is essential for maintaining vascular tone and preventing inflammation. This binding also increases the expression of adhesion molecules, promoting the adhesion of leukocytes to the endothelium, a key step in the initiation of atherosclerosis [17, 24]. |
| Trigger oxidative stress in vascular cells | Ox-LDL can also trigger oxidative stress in vascular cells, leading to further damage and contributing to the progression of atherosclerotic lesions [21]. |
| Macrophage activation and foam cell formation | Ox-LDL is taken up by macrophages through LOX-1, leading to the accumulation of lipids within the cells, forming foam cells. These foam cells contribute to the formation of atherosclerotic plaques [46]. |
| Stimulation of smooth muscle cell proliferation and migration | Ox-LDL promotes the proliferation and migration of smooth muscle cells, which are crucial for the development of atherosclerotic plaques and the thickening of the arterial wall [47]. |
| Induction of inflammation | Ox-LDL triggers inflammation by activating macrophages and other immune cells, leading to the release of cytokines and chemokines that further promote the recruitment of inflammatory cells to the atherosclerotic lesion [48]. |
| Modulation of inflammation-related pathways | Ox-LDL modulates inflammation-related molecular pathways, including the regulation of microRNAs and activation of the NLRP3 inflammasome [49]. |
| Plaque instability and thrombosis | Ox-LDL contributes to the instability of atherosclerotic plaques by inducing the production of metalloproteinases, which can lead to the rupture of plaques and the formation of thrombi, which can cause acute cardiovascular events [50]. |
| Regulation of macrophage polarization | Ox-LDL regulates macrophage polarization, it can induce macrophage polarization through various mechanisms, including cell signaling, metabolic reprogramming, epigenetics, and intercellular communication, which promotes vessel wall inflammation and aggravates the progression of atherosclerosis [51]. |
| Arterial stiffening | Ox-LDL may also play a role in arterial stiffening, which is associated with increased cardiovascular risk [52]. |
LOX-1: oxidized low-density lipoprotein receptor-1
