Differential Telomere Shortening in Blood versus Arteries in an Animal Model of Type 2 Diabetes.
Vascular dysfunction is an early feature of diabetic vascular disease, due to increased oxidative stress and reduced nitric oxide (NO) bioavailability. This can lead to endothelial cell senescence and clinical complications such as stroke. Cells can become senescent by shortened telomeres and oxidative stress is known to accelerate telomere attrition. Sirtuin 1 (SIRT1) has been linked to vascular health by upregulating endothelial nitric oxide synthase (eNOS), suppressing oxidative stress, and attenuating telomere shortening. Accelerated leukocyte telomere attrition appears to be a feature of clinical type 2 diabetes (T2D) and therefore the telomere system may be a potential therapeutic target in preventing vascular complications of T2D. However the effect of T2D on vascular telomere length is currently unknown. We hypothesized that T2D gives rise to shortened leukocyte and vascular telomeres alongside reduced vascular SIRT1 expression and increased oxidative stress. Accelerated telomere attrition was observed in circulating leukocytes, but not arteries, in T2D compared to control rats. T2D rats had blunted arterial SIRT1 and eNOS protein expression levels which were associated with reduced antioxidant defense capacity. Our findings suggest that hyperglycemia and a deficit in vascular SIRT1 per se are not sufficient to prematurely shorten vascular telomeres.
Discipline of Biotechnology, School of Medicine, Flinders University, Bedford Park, SA 5042, Australia.
Samira
S
Tajbakhsh
Discipline of Biotechnology, School of Medicine, Flinders University, Bedford Park, SA 5042, Australia.
Kamelya
K
Aliakbari
Discipline of Surgery, School of Medicine, Flinders University, Bedford Park, SA 5042, Australia.
Damian J
DJ
Hussey
Discipline of Haematology, School of Medicine, Flinders University, Bedford Park, SA 5042, Australia.
Karen M
KM
Lower
Department of Internal Medicine, University of Utah, Salt Lake City, UT 84132, USA.
Anthony J
AJ
Donato
Discipline of Human Physiology, School of Medicine, Flinders University, Bedford Park, SA 5042, Australia.
Elke M
EM
Sokoya
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001158:Arteries / Q000473:pathology*; D001794:Blood Pressure; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000378:metabolism; D006943:Hyperglycemia / Q000473:pathology; D007962:Leukocytes / Q000166:cytology / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D018384:Oxidative Stress; D010641:Phenotype; D051381:Rats; D017208:Rats, Wistar; D056564:Sirtuin 1 / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D016615:Telomere / Q000648:ultrastructure*; D059506:Telomere Shortening
D000975:Antioxidants; D013481:Superoxides; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; C488368:Sirt1 protein, rat; D056564:Sirtuin 1