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Sci Rep ; 10(1): 12220, 2020 07 22.
Article in English | MEDLINE | ID: mdl-32699285

ABSTRACT

Growing evidence supports the role of advanced glycation end products (AGEs) in the development of diabetic vascular complications and cardiovascular diseases (CVDs). We have shown that high-molecular-weight AGEs (HMW-AGEs), present in our Western diet, impair cardiac function. Whether HMW-AGEs affect vascular function remains unknown. In this study, we aimed to investigate the impact of chronic HMW-AGEs exposure on vascular function and structure. Adult male Sprague Dawley rats were daily injected with HMW-AGEs or control solution for 6 weeks. HMW-AGEs animals showed intracardiac pressure overload, characterized by increased systolic and mean pressures. The contraction response to PE was increased in aortic rings from the HMW-AGEs group. Relaxation in response to ACh, but not SNP, was impaired by HMW-AGEs. This was associated with reduced plasma cyclic GMP levels. SOD restored ACh-induced relaxation of HMW-AGEs animals to control levels, accompanied by a reduced half-maximal effective dose (EC50). Finally, collagen deposition and intima-media thickness of the aortic vessel wall were increased with HMW-AGEs. Our data demonstrate that chronic HMW-AGEs exposure causes adverse vascular remodelling. This is characterised by disturbed vasomotor function due to increased oxidative stress and structural changes in the aorta, suggesting an important contribution of HMW-AGEs in the development of CVDs.


Subject(s)
Acetaldehyde/analogs & derivatives , Aorta/metabolism , Aorta/physiopathology , Blood Pressure/physiology , Heart/physiopathology , Vascular Remodeling/physiology , Acetaldehyde/metabolism , Acetylcholine/pharmacology , Animals , Aorta/drug effects , Blood Pressure/drug effects , Cardiovascular Diseases/metabolism , Cardiovascular Diseases/physiopathology , Collagen/metabolism , Cyclic GMP/metabolism , Endothelium, Vascular/drug effects , Endothelium, Vascular/metabolism , Endothelium, Vascular/physiopathology , Glycation End Products, Advanced/metabolism , Heart/drug effects , Male , Oxidation-Reduction/drug effects , Oxidative Stress/drug effects , Oxidative Stress/physiology , Rats , Rats, Sprague-Dawley , Superoxide Dismutase/metabolism , Vascular Remodeling/drug effects , Vasoconstriction/drug effects , Vasoconstriction/physiology , Vasodilation/drug effects , Vasodilation/physiology
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