1. Glycolaldehyde-modified proteins cause adverse functional and structural aortic remodeling leading to cardiac pressure overload.
- Author
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Haesen S, Cöl Ü, Schurgers W, Evens L, Verboven M, Driesen RB, Bronckaers A, Lambrichts I, Deluyker D, and Bito V
- Subjects
- 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, Acetaldehyde analogs & derivatives, Aorta metabolism, Aorta physiopathology, Blood Pressure physiology, Heart physiopathology, Vascular Remodeling physiology
- 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 (EC
50 ). 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.- Published
- 2020
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