Therapeutic Targeting of the Proinflammatory IL-6-JAK/STAT Signalling Pathways Responsible for Vascular Restenosis in Type 2 Diabetes Mellitus

Figure 1

Cellular and molecular signals linking type 2 diabetes mellitus and neointimal hyperplasia. Type 2 diabetes is associated with circulating hyperglycaemia and hyperinsulinaemia and increased proinflammatory cytokines. Activated endothelial cells upregulate MCP-1, ICAM-1, VCAM-1, and E-selectin. This increases recruitment of platelets and leukocytes which release IL-6. This key cytokine acts on smooth muscle cells to activate JAK/STAT signalling to trigger upregulation of cyclin D1 and matrix metalloproteinases (MMPs) and further increase MCP-1 and ICAM-1 induction. These molecular signatures are characteristic of synthetic smooth muscle cells, leading to the development of neointimal hyperplasia.