Fig. 7
From: Targeting integrin pathways: mechanisms and advances in therapy
Main roles of integrins in the process of AS. Integrin signaling can affect multiple processes in AS, including endothelial dysfunction and activation, leukocyte homing to the plaque, smooth muscle cell migration, and thrombosis. In the process of endothelial cell activation, ox-LDL activates α5β1, induces the FAK/ERK/p90RSK pathway and promotes NF-κB signaling. Shear stress can activate αvβ3 and induce PAK activation by binding to fibronectin, thereby promoting NF-κB activation. Both ox-LDL and shear stress generated by blood flow mediate the increased expression of proinflammatory genes (ICAM-1 and VCAM-1) after integrin ligation. During the process of leukocyte homing to plaques, αxβ2 and α4β1 interact with VCAM-1 on the endothelial cell surface, and αxβ2 and αLβ2 interact with ICAM-1 to promote leukocyte adhesion. Integrins α4β1, α9β1 and αvβ3 on the surface of monocytes interact with osteopontin, which is expressed in atherosclerotic plaques, to promote monocyte migration and survival. Integrin αDβ2 is upregulated during macrophage foam cell formation. During vascular smooth muscle cell migration, αvβ3 binding with fibronectin, osteopontin, etc., mediates FAK activity and drives migration. In the process of thrombosis, integrins α2β1 and aIIbβ3 on platelets are involved in platelet adhesion, activation, aggregation, and thrombosis
