Diabetic macroangiopathy: Pathogenetic insights and novel therapeutic approaches with focus on high glucose-mediated vascular damage

Diabetic macroangiopathy - a specific form of accelerated atherosclerosis - is characterized by intra-plaque new vessel formation due to excessive/abnormal neovasculogenesis and angiogenesis, increased vascular permeability of the capillary vessels, and tissue edema, resulting in frequent atherosclerotic plaque hemorrhage and plaque rupture. Mechanisms that may explain the premature and rapidly progressive nature of atherosclerosis in diabetes are multiple, and to a large extent still unclear. However, mechanisms related to hyperglycemia certainly play an important role. These include a dysregulated vascular regeneration. In addition, oxidative and hyperosmolar stresses, as well as the activation of inflammatory pathways triggered by a dysregulated activation of membrane channel proteins aquaporins, have been recognized as key events. Here, we review recent knowledge of cellular and molecular pathways of macrovascular disease related to hyperglycemia in diabetes. We also here highlight how new insights into pathogenic mechanisms of vascular damage in diabetes may indicate new targets for prevention and treatment.