Insights into the molecular mechanisms of diabetes-induced endothelial dysfunction: focus on oxidative stress and endothelial progenitor cells.
Diabetes mellitus is a heterogeneous, multifactorial, chronic disease characterized by hyperglycemia owing to insulin insufficiency and insulin resistance (IR). Recent epidemiological studies showed that the diabetes epidemic affects 382 million people worldwide in 2013, and this figure is expected to be 600 million people by 2035. Diabetes is associated with microvascular and macrovascular complications resulting in accelerated endothelial dysfunction (ED), atherosclerosis, and cardiovascular disease (CVD). Unfortunately, the complex pathophysiology of diabetic cardiovascular damage is not fully understood. Therefore, there is a clear need to better understand the molecular pathophysiology of ED in diabetes, and consequently, better treatment options and novel efficacious therapies could be identified. In the light of recent extensive research, we re-investigate the association between diabetes-associated metabolic disturbances (IR, subclinical inflammation, dyslipidemia, hyperglycemia, dysregulated production of adipokines, defective incretin and gut hormones production/action, and oxidative stress) and ED, focusing on oxidative stress and endothelial progenitor cells (EPCs). In addition, we re-emphasize that oxidative stress is the final common pathway that transduces signals from other conditions-either directly or indirectly-leading to ED and CVD.
Department of Biochemistry, Medical Research Institute, Alexandria University, Alexandria, Egypt. m.ibrahim1988@hotmail.com.|Hudson Institute of Medical Research, School of Clinical Sciences, Monash University, Melbourne, VIC, Australia. m.ibrahim1988@hotmail.com.
Mohamed I
http://orcid.org/0000-0002-4855-2360
MI
Saad
Department of Human Genetics, Medical Research Institute, Alexandria University, Alexandria, Egypt.
Taha M
TM
Abdelkhalek
Department of Human Genetics, Medical Research Institute, Alexandria University, Alexandria, Egypt.
Moustafa M
MM
Saleh
Department of Biochemistry, Medical Research Institute, Alexandria University, Alexandria, Egypt.
Maher A
MA
Kamel
Department of Human Genetics, McGill University, Montreal, QC, Canada.
Mina
M
Youssef
Department of Molecular Medicine, University of Padova, Padua, Italy.
Shady H
SH
Tawfik
Department of Biomedical Sciences, Copenhagen University, Copenhagen, Denmark.
Helena
H
Dominguez
D054392:Adipokines / Q000502:physiology; D000818:Animals; D003920:Diabetes Mellitus / Q000378:metabolism* / Q000503:physiopathology; D050171:Dyslipidemias / Q000378:metabolism; D066026:Endothelial Progenitor Cells / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000503:physiopathology*; D054439:Ghrelin / Q000502:physiology; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism; D054795:Incretins / Q000502:physiology; D007249:Inflammation / Q000378:metabolism; D007333:Insulin Resistance; D018384:Oxidative Stress
D054392:Adipokines; D054439:Ghrelin; D054795:Incretins
Diabetes; Endothelial dysfunction; Endothelial progenitor cells; Oxidative stress