Abstract
BackgroundDiabetes mellitus in elderly represents an exceptional subset in the population vulnerable to cardiovascular events. As aging, diabetes mellitus and hypertension share common pathways, an ideal treatment should possess the ability to counter more than one of, if not all, the underlying mechanisms. Stem cells emerged as a potential approach for complicated medical problems. We tested here the possible role of trans-differentiated endothelial cells (ECs) in the treatment of diabetes mellitus in old rats.MethodsMesenchymal stem cells where isolated from umbilical cord Wharton’s Jelly and induced to differentiate into endothelial like-cells using vascular endothelial growth factor-enriched media. Thirty aged male Wistar albino rats were used in the present study. Rats were divided (10/group) into: control group (18–20 months old, weighing 350–400 g, received single intraperitoneal injection as well as single intravenous injection via tail vein of the vehicles), aged diabetic group (18–20 months old, weighing 350–400 g, received single intraperitoneal injection of 50 mg/kg streptozotocin, and also received single intravenous injection of saline via tail vein), and aged diabetic + ECs group (18–20 months old, weighing 350–400 g, received single intraperitoneal injection of 50 mg/kg streptozotocin, and also received single intravenous injection of 2*106 MSC-derived ECs in 0.5 ml saline via tail vein) groups. Assessment of SBP, aortic PWV, and renal artery resistance was performed. Serum levels of ET1, ANG II, IL-6, TNF-α, MDA, ROS, and VEGF were evaluated, as well as the aortic NO tissue level and eNOS gene expression. Histopathological and immunostaining assessments of small and large vessels were also performed.ResultsInduction of diabetes in old rats resulted in significant increase in SBP, aortic PWV, renal artery resistance, and serum levels of ET1, ANG II, IL-6, TNF-α, MDA, ROS, and VEGF. While there was significant decrease in aortic NO tissue level and eNOS gene expression in the aged diabetic group when compared to aged control group. ECs treatment resulted in significant improvement of endothelial dysfunction, inflammation and oxidative stress.ConclusionWe report here the potential therapeutic role of trans-differentiated ECs in aged diabetics. ECs demonstrated anti-inflammatory, antioxidant, gene modifying properties, significantly countered endothelial dysfunction, and improved vascular insult.
Highlights
Diabetes mellitus in elderly represents an exceptional subset in the population vulnerable to cardiovascular events
This is most obvious from the attenuation of endothelium-dependent dilator responses, which is a consequence of the alteration in the expression and/ or activity of the endothelial nitric oxide (NO) synthase, upregulation of the inducible NO synthase, and increased oxidative stress
Aging is associated with a reduction in the regenerative capacity of the endothelium and endothelial senescence, which is characterized by an increased rate of endothelial cell apoptosis [2]
Summary
Diabetes mellitus in elderly represents an exceptional subset in the population vulnerable to cardiovascular events. Apart from ageassociated changes of the vascular wall, which includes luminal enlargement, increased intimal and medial thickness, and vascular stiffness, endothelial function declines with age [1] This is most obvious from the attenuation of endothelium-dependent dilator responses, which is a consequence of the alteration in the expression and/ or activity of the endothelial NO synthase (eNOS), upregulation of the inducible NO synthase (iNOS), and increased oxidative stress. Studies have shown that endothelial dysfunction, as represented by impaired endothelium-dependent nitric oxide (NO)-mediated relaxation, occurs in diabetes. Mechanisms underlying this endothelial dysfunction could include decreased activity and/or expression of eNOS or increased degradation of NO secondary to enhanced superoxide production [4]
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