Circulating Progenitor Cells in Diabetic Vascular Disease

Abstract

Patients with diabetes have altered levels and function of (bone marrow-derived) vascular progenitor cells (endothelial progenitor cells-EPC, smooth muscle progenitor cells-SPC) which may contribute to their accelerated atherosclerosis. The results from clinical and experimental studies in this thesis give insight into vascular progenitor cell dysfunction and availability in patients with diabetes together with further comprehension of diabetes-associated atherosclerosis. This is of significance to create therapeutic strategies to prevent the onset or further development of diabetes-associated vascular complications. Furthermore, the outcome of clinical trials that use patients’ own bone marrow cells to stimulate vascular regeneration or the outcome of cell mobilization studies may be limited because of functional impairment of the cells. We identified signaling pathways in EPC that are affected by diabetes and showed that they can be regulated by folic acid. These pathways are possible therapeutic targets in EPC dysfunction and of interest to investigate in further detail. Furthermore, current strategies in progenitor cell therapy may also influence SPC availability either in a beneficial or detrimental way. We showed that SPC play a role in the accelerated atherosclerosis development in diabetes and that circulating SPC may be involved in other types of adverse tissue remodeling such as renal fibrosis. Intervening in SPC availability by altering progenitor cell differentiation towards the endothelial lineage is a therapeutic option in enhancing vascular repair and preventing tissue damage. Modulating circulating progenitor cell function and availability represents a field of opportunities that can lead to attenuation of the development of diabetes-associated vascular disease.