Pathobiology of Endothelial and Other Vascular Cells in Diabetes Mellitus: Call for Data

Because the pathogenetic understanding of diabetic vascular complications remains fragmentary, and even the best available interventions may prove insufficient to arrest the progression of certain lesions, new avenuses of investigation should be pursued. One of these should be the early in vivo investigation of the cells that endure the pathological process (pericytes and endothelial and mesangial cells), preferably in humans. The abnormal vascular architecture (i.e., capillary acellularity, microaneurysms, thickened basement membranes, and mesangial expansion) and the hemostatic and hemodynamic alterations observed in diabetes point to an adaptive/maladaptive replicative and biosynthetic program triggered by the metabolic perturbation, but positive documentation of cellular changes in vivo remains grossly insufficient. Critical review of current knowledge of microangiopathy permits elaboration of specific questions that, with the tools provided by the new molecular technology, may be posed about vascular cells in situ. Knowing whether and how the cell types involved in the vascular complications of diabetes modify their differentiated functions may offer novel targets for intervention and, most important, should provide a much needed “sounding board” against which to test the viability and refine the focus of pathogenetic hypotheses.