Significance of Endothelial Progenitor Cells in Subjects With Diabetes
- Gian Paolo Fadini, MD1,
- Saverio Sartore, PHD2,
- Carlo Agostini, MD1 and
- Angelo Avogaro, MD, PHD1
- 1Department of Clinical and Experimental Medicine, University of Padova Medical School, Padova, Italy
- 2Department of Biomedical Sciences, University of Padova Medical School, Padova, Italy
- Address correspondence and reprint requests to Prof. Angelo Avogaro, MD, PhD, or Gian Paolo Fadini, Policlinico Universitario, Dipartimento di Medicina Clinica e Sperimentale, Malattie del Metabolismo, via Giustiniani, 2–35100 Padova, Italy. E-mail: Prof. Angelo Avogaro, angelo.avogaro{at}unipd.it. Or Gian Paolo Fadini, gianpaolofadini{at}hotmail.com
- ADMA, asymmetric dimethylarginine
- CKD, chronic kidney disease
- EPC, endothelial progenitor cell
- HIF, hypoxia-inducible factor
- PAD, peripheral arterial disease
- PBMC, peripheral blood mononuclear cell
- PI, phosphatidylinositol
- ROS, reactive oxygen species
- SDF, stromal-derived factor
- VEGF, vascular endothelial growth factor
Diabetes complications represent a huge burden for patients and health services. The fight against each single complication has led to significant improvements in diabetes care, especially for microvascular complications, yet macroangiopathy remains a major source of morbidity and mortality. A common approach for the prevention and treatment of diabetes complications relies on the understanding of their complex pathophysiology. A unifying biochemical theory suggests that oxidative stress underlies subsequent cellular damage pathways, which leads to diabetes complications, but common supracellular mechanisms are still unclear. Endothelial progenitor cells (EPCs) are circulating immature cells that contribute to vascular homeostasis and compensatory angiogenesis. During the last decade, data have become available indicating that alterations in EPCs may have an important causative role in the development and progression of virtually all diabetes complications. In this review, we will focus on the mechanisms of EPC reduction and dysfunction associated with diabetes by discussing their role in each single complication and possible therapeutic interventions.
A unified pathogenesis of late diabetes complications
Diabetes is associated with a unique constellation of disabling complications. While it was originally thought that a single patient tends to develop the cluster of micro- or macrovascular complications, recent prospective studies show that typical markers of microvascular dysfunction, such as microalbuminuria or retinal vascular abnormalities, are associated with an increased risk of macrovascular events (1,2). These and other data suggest that there must be a unifying pathogenetic model underlying diabetes complications. To date, the most credited and supported model proposes that oxidative stress originating from mitochondria activates all subcellular damage pathways (3). However, subsequent events diverge for each complication, and there is not a supracellular unifying hypothesis.
The discovery that a subset of circulating immature cells contributes to vascular homeostasis has been a major achievement in many fields of basic science. In this review, we will focus the attention on …
