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INTRODUCTION
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 [...]
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