Structural modifications in the arterial wall during physiological aging and as a result of diabetes mellitus in a mouse model: Are the changes comparable?

• Published in: Diabetes & metabolism Vol. 37; no. 2; pp. 106 - 111
• Main Authors: Prévost, G, Bulckaen, H, Gaxatte, C, Boulanger, E, Béraud, G, Creusy, C, Puisieux, F, Fontaine, P
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 01-04-2011
• Subjects: Acetylcholine - pharmacology; Aging - physiology; Animals; Aorta - chemistry; Aorta - pathology; Aorta - physiopathology; Arteries - pathology; Arteries - physiopathology; Diabetes; Diabetes Mellitus, Experimental - pathology; Diabetes Mellitus, Experimental - physiopathology; Diabète; Endocrinology & Metabolism; Endothelium; Endothelium, Vascular - physiopathology; Endothélium; Internal Medicine; Intima/media; Intima/média; Male; Mice; Mice, Inbred C57BL; Muscle Contraction - drug effects; Muscle Relaxation - drug effects; Muscle, Smooth, Vascular - pathology; Muscle, Smooth, Vascular - physiopathology; Phenylephrine - pharmacology; Receptor for Advanced Glycation End Products; Receptors, Immunologic - analysis; Vascular aging; Vasodilatation; Vieillissement vasculaire; Vascular aging; Intima/media; Vieillissement vasculaire; Endothélium; Vasodilatation; Diabète; Diabetes; Intima/média; Endothelium
• ISSN: 1262-3636; 1878-1780
• DOI: 10.1016/j.diabet.2010.08.005

Abstract Aim Vascular accelerated aging represents the major cause of morbidity and mortality in subjects with diabetes mellitus. In the present study, our aim was to compare premature functional and morphological changes in the arterial wall resulting from streptozotocin (STZ)-induced diabetes mellitus in mice over a short-term period with those that develop during physiological aging. The effect of aminoguanidine (AG) on the prevention of these alterations in the diabetic group was also analyzed. Methods The vascular relaxation response to acetylcholine (ACh) in the mouse was tested in isolated segments of phenylephrine (Phe)-precontracted aorta at 2, 4 and 8 weeks (wk) of STZ-induced diabetes and compare to 12- and 84-wk-old mice. Aortic structural changes were investigated, and receptor for AGE (RAGE) aortic expression was quantified by western blot. Results Compared to the 12-wk control group (76 ± 5%), significant endothelium-dependant relaxation (EDR) impairment was found in the group of 12-wk-old mice, which underwent a 4-wk diabetes-inducing STZ treatment (12wk-4WD) (52 ± 4%; P < 0.01) and was yet more apparent in the group of 16-wk-old mice, which underwent an 8-wk diabetes-inducing STZ treatment (16wk-8WD) (34 ± 4%; P < 0.001). The alteration in EDR was relatively comparable between the diabetic 12wk-4WD group and the 84-wk-old group (52.7 ± 4 vs. 48 ± 4%). Intima/media aortic thickening and aortic structural changes were significantly increased in the diabetic 12wk-4WD group and were even more apparent in the 84-wk group compared to the 12-wk controls. AG treatment in the 12wk-4WD + AG diabetic group significantly improved EDR, decreased RAGE expression and showed an aging preventive effect on the structural changes of the arterial wall. Conclusion Our study compared EDR linked to physiological aging with that observed in the case of STZ-induced diabetes over a short-term period, and demonstrated the beneficial effect of AG.