The Entry and Egress of Monocytes in Atherosclerosis: A Biochemical and Biomechanical Driven Process

Figure 2

Impact of Netrin-1 and Semaphorins on the entry and egress of monocytes and macrophages in the progression of atherosclerosis. Atherosclerosis-induced local inflammation causes hypoxia, which in turn mediates the release of HIF-1α. HIF-1α could subsequently upregulate the expression of Netrin-1 and its receptor UNC5b in both macrophages and endothelial cells. Netrin-1 secreted by foam cells and macrophages could inactivate macrophage migration through its receptor UNC5b and prevent its egress from the plaque simultaneously. It could also enhance the recruitment of SMCs and promote lesion progression. However, Netrin-1 secreted by endothelial cell could make a beneficial contribution to the progression of atherosclerosis by preventing monocyte chemotaxis through binding with α₆β₄ and α₃β₁ integrin. Semaphorin 3A inhibits the migration of monocyte to CX3CL1 and its adhesion to endothelial cells. Semaphorin 3E is secreted by macrophages, which could depress the migration of macrophages to chemokines like CCL19 and CCL21.