title: Type 2 diabetes aggravates Alzheimer's disease-associated vascular alterations of the aorta in mice.
abstract: Vascular risk factors are associated with a higher incidence of dementia. In fact, diabetes mellitus is considered a main risk factor for Alzheimer's disease (AD) and both diseases are characterized by vascular dysfunction. However, the underlying mechanisms remain largely unknown. Here, the effects of high-sucrose-induced type 2 diabetes (T2D) in the aorta of wild type (WT) and triple-transgenic AD (3xTg-AD) mice were investigated. 3xTg-AD mice showed a significant decrease in body weight and an increase in postprandial glycemia, glycated hemoglobin (HbA1c), and vascular nitrotyrosine, superoxide anion (O2•-), receptor for the advanced glycation end products (RAGE) protein, and monocyte chemoattractant protein-1 (MCP-1) levels when compared to WT mice. High-sucrose intake caused a significant increase in body weight, postprandial glycemia, HbA1c, triglycerides, plasma vascular cell adhesion molecule 1 (VCAM-1), and vascular nitrotyrosine, O2•-, RAGE, and MCP-1 levels in both WT and 3xTg-AD mice when compared to the respective control group. Also, a significant decrease in nitric oxide-dependent vasorelaxation was observed in 3xTg-AD and sucrose-treated WT mice. In conclusion, AD and T2D promote similar vascular dysfunction of the aorta, this effect being associated with elevated oxidative and nitrosative stress and inflammation. Also, AD-associated vascular alterations are potentiated by T2D. These findings support the idea that metabolic alterations predispose to the onset and progression of dementia.
authors.affiliation: Institute of Physiology, Faculty of Medicine, University of Coimbra, Coimbra, Portgual IBILI - Institute of Biomedical Imaging and Life Sciences, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
authors.forename: Cristina M
authors.initials: CM
authors.lastname: Sena
authors.affiliation: Institute of Physiology, Faculty of Medicine, University of Coimbra, Coimbra, Portgual IBILI - Institute of Biomedical Imaging and Life Sciences, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Pereira
authors.affiliation: CNC - Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.
authors.forename: Cristina
authors.initials: C
authors.lastname: Carvalho
authors.affiliation: IBILI - Institute of Biomedical Imaging and Life Sciences, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
authors.forename: Rosa
authors.initials: R
authors.lastname: Fernandes
authors.affiliation: Institute of Physiology, Faculty of Medicine, University of Coimbra, Coimbra, Portgual IBILI - Institute of Biomedical Imaging and Life Sciences, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
authors.forename: Raquel M
authors.initials: RM
authors.lastname: Seiça
authors.affiliation: Institute of Biochemistry, Faculty of Medicine, University of Coimbra, Coimbra, Portugal CNC - Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.
authors.forename: Catarina R
authors.initials: CR
authors.lastname: Oliveira
authors.affiliation: Institute of Physiology, Faculty of Medicine, University of Coimbra, Coimbra, Portgual CNC - Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.
authors.forename: Paula I
authors.initials: PI
authors.lastname: Moreira
mesh_terms: D000109:Acetylcholine / Q000378:metabolism / Q000494:pharmacology; D000544:Alzheimer Disease / Q000150:complications* / Q000235:genetics / Q000473:pathology*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000704:Analysis of Variance; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D004195:Disease Models, Animal; D019332:Endothelin-1 / Q000378:metabolism; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D009599:Nitroprusside / Q000494:pharmacology; D053764:Presenilin-1 / Q000235:genetics; D013482:Superoxide Dismutase / Q000378:metabolism; D014665:Vasodilator Agents / Q000494:pharmacology; D016875:tau Proteins / Q000235:genetics
chemical_list: D016564:Amyloid beta-Protein Precursor; D019332:Endothelin-1; C508853:PSEN1 protein, human; D053764:Presenilin-1; D014665:Vasodilator Agents; D016875:tau Proteins; D009599:Nitroprusside; D013482:Superoxide Dismutase; D000109:Acetylcholine
keywords: Alzheimer's disease; aorta; endothelium; inflammation; oxidative stress; type 2 diabetes