The first stage of atherosclerosis is believed to be endothelial dysfunction. The features of the earliest stage of atherosclerosis are the expression of lectin-like oxidized-low-density-lipoprotein receptor-1 (LOX-1), vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1).
Oxidised low-density lipoprotein (oxLDL) is crucial in the trigger and evolution of atherosclerosis. The main endothelial receptor of oxLDL, LOX-1, is responsible for adhering, internalisation, and degradation of oxLDL in endothelial cells. Both invitro and invivo experiments have demonstrated the receptor to be crucial in the initiation of atherosclerosis and to be upregulated by pro-atherogenic factors, for example. shear stress, tumour necrosis factor (TNF)-α, and oxLDL itself.
In addition, VCAM-1 and ICAM-1 also play crucial roles in the process of coronary artery disease as they’re critical to leukocyte adherence, rolling, and trans-endothelial migration. VCAM-1 is mainly an inducible molecule, whereas ICAM-1 is also constitutively expressed on resting endothelial cells. They are both up-regulated by pro-atherogenic agents. VCAM-1 has, based on experiments with knockout mice, been recognised as the major adherence molecule in the trigger of atherosclerosis. A high degree of soluble ICAM-1 (sICAM-1) in plasma has been linked to increased risk of cardiovascular events, as well as to cancer and autoimmune disorders.
