Cellular and molecular mechanisms of vascular injury in diabetes — Part II: Cellular mechanisms and therapeutic targets

Although the mechanisms by which insulin-resistance and hyperglycemia lead to cardiovascular disease are still incompletely understood, all mechanisms apparently converge on the vessel wall and the endothelium as a common disease target. Endothelial cells play a crucial role in vascular homeostasis, providing a functional barrier and modulating several signals involved in vasomotion, as well as antiplatelet, anti-inflammatory, anti-proliferative, and anti-oxidant properties of the vessel wall. Endothelial cell dysfunction occurs early in diabetes and insulin resistance states. Since atherosclerosis may result from an imbalance between the magnitude of vascular injury and the capacity of repair, a role has been recently postulated for a defective mobilization of vascular progenitors, including endothelial progenitor cells, in the pathogenesis of vascular disease. Here we summarize the evidence for such an occurrence. We also here highlight how new insights into pathways of vascular damage in diabetes may indicate new targets for preventive and treatment strategies.

Graphical AbstractAlthough the mechanisms by which insulin-resistance and hyperglycemia lead to cardiovascular disease are still incompletely understood, all mechanisms apparently converge on the vessel wall and the endothelium as a common disease target. Endothelial cells play a crucial role in vascular homeostasis, providing a functional barrier and modulating several signals involved in vasomotion, as well as antiplatelet, anti-inflammatory, anti-proliferative, and anti-oxidant properties of the vessel wall. Endothelial cell dysfunction occurs early in diabetes and insulin resistance states. Since atherosclerosis may result from an imbalance between the magnitude of vascular injury and the capacity of repair, a role has been recently postulated for a defective mobilization of vascular progenitors, including endothelial progenitor cells, in the pathogenesis of vascular disease. Here we summarize the evidence for such an occurrence and highlight how new insights on pathways of vascular damage in diabetes may indicate new targets for prevention and treatment.Figure optionsDownload as PowerPoint slide