Figure 1.

Immune mechanisms engaged in diabetes-accelerated atherosclerosis. Diabetes-associated hyperglycemia, hyperlipidemia, and oxidative stress render the endothelium dysfunctional, leading to the retention and oxidation of LDL molecules in the intimal space. The increased expression of adhesion molecules E-selectin, ICAM-1, VCAM-1 at the endothelial membrane, and upregulation of chemotactic molecules such as MCP-1 facilitate the continuous infiltration of immune cells to the inflamed aorta. Resident and monocyte-derived macrophages engulf LDL to form foam cells which release a host of pro-inflammatory cytokines, protease, and ROS. Activated T cells recruited from the circulation to the lesion also secrete cytokines which amplify pro-inflammatory cellular immune responses in the diabetic plaque. The diabetes-mediated increase in vascular inflammation drives the development and progression of atherosclerosis. AGEs, advanced glycation end-products; AT1R, angiotensin II type 1 receptor; ICAM-1, intercellular adhesion molecule-1; LDL, low-density lipoprotein; MCP-1, monocyte chemotactic protein-1; RAGE, receptor for advanced glycation end products; ROS, reactive oxygen species; VCAM-1, vascular cell adhesion molecule-1.