Vascular repair strategies in type 2 diabetes: novel insights

The maintenance of blood vessel function throughout life requires the continuous replacement of lost or dysfunctional cells as well as the adaptation to changing physiologic or pathologic stimuli, including changes in local oxygen demand, varying amounts of pro- or anti-inflammatory agents, or injury. Over decades, those mechanisms fulfill their function unnoticed. Repetitive challenge of vascular regenerative mechanisms by lifestyle-mediated cues, including the intake of noxious substances and lipids, as well as insufficient physical activity, evokes a gradual exhaustion and dysregulation of reparative pathways over the years (Figure 1). The impairment of cellular function—affecting resident vascular cells as well as “accessory” cells—is associated with the development of microvascular and macrovascular dysfunction. The resulting clinical manifestations include microvascular rarefaction in the limbs, myocardium, kidneys and bone marrow, causing the loss of the affected limb and/or dysfunction of the organ, impaired wound healing and altered hematopoiesis. Macrovascular dysfunction increases the risk for myocardial, cerebral or peripheral occlusive events through atherosclerotic vascular remodeling, endothelial erosion and, finally thrombotic events