Over recent years, the explosive increase in the worldwide prevalence of
type 2 diabetes has transformed this disease into a major public health concern.
Cardiovascular complications are the leading causes of morbidity in diabetic patients,
whose cardiovascular mortality risk is up to four times higher than in non-diabetic
subjects. Morphological and structural changes in large and small vessels are usually
preceded by alterations in endothelial function, resulting from the unbalanced
production of endothelial-derived vascular mediators. Metabolic disturbances including
hyperglycemia, insulin resistance, hyperinsulinemia and dyslipidemia all contribute to
endothelial dysfunction via both distinct and overlapping mechanisms. In turn,
abnormal synthesis and release of endothelial mediators may contribute to exacerbate
the impaired function of metabolic tissues, thus creating a vicious circle where these
conditions reciprocally reinforce and worsen each other. Increasing understanding on
mechanisms underlying endothelial dysfunction in diabetes may serve to identify
potential therapeutic targets, and help to develop novel therapeutic approaches for
reducing cardiovascular risk rate in diabetic patients. This chapter summarizes the
current knowledge on the most recently identified targets and therapies for the treatment
of diabetes and its cardiovascular complications.
Keywords: Advanced glycation-end products (AGEs), AMP-activated protein
kinase (AMPK), diabetes, dipeptidyl peptidase-4 enzyme (DPP4), endothelial
dysfunction, endothelial progenitor cells (EPC), endothelin-1 (ET-1), flood
mediated dilation (FMD), glucagon-like peptide 1 (GLP-1), nitric oxide (NO),
poly (ADP ribose) polymerase 1 (PARP-1), protein kinase C (PKC), reactive
oxygen species (ROS), rho-associated kinase (ROCK), sodium-glucose cotrasporter-
2 (SGLT-2), therapeutic strategies, thiazolidine-2-4-diones (TZDs),
vascular endothelial growth factor (VEGF).
