title: Diabetic Nephropathy Induced by Increased Ace Gene Dosage Is Associated with High Renal Levels of Angiotensin (1-7) and Bradykinin.
abstract: Population studies have shown an association between diabetic nephropathy (DN) and insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene (ACE in humans, Ace in mice). The aim was to evaluate the modulation of Ace copies number and diabetes mellitus (DM) on renal RAS and correlate it with indicators of kidney function. Increased number of copies of the Ace gene, associated with DM, induces renal dysfunction. The susceptibility to the development of DN in 3 copies of animals is associated with an imbalance in activity of RAS enzymes leading to increased synthesis of Ang II and Ang-(1-7). Increased concentration of renal Ang-(1-7) appears to potentiate the deleterious effects triggered by Ang II on kidney structure and function. Results also show increased bradykinin concentration in 3 copies diabetic group. Taken together, results indicate that the deleterious effects described in 3 copies diabetic group are, at least in part, due to a combination of factors not usually described in the literature. Thus, the data presented here show up innovative and contribute to understanding the complex mechanisms involved in the development of DN, in order to optimize the treatment of patients with this complication.
authors.affiliation: Nephrology Division, Department of Medicine, Federal University of São Paulo, Rua Botucatu 740, Vila Clementino, 04023-900 São Paulo, SP, Brazil.
authors.forename: Nádia
authors.initials: N
authors.lastname: Bertoncello
authors.affiliation: Nephrology Division, Department of Medicine, Federal University of São Paulo, Rua Botucatu 740, Vila Clementino, 04023-900 São Paulo, SP, Brazil.
authors.forename: Roseli Peres
authors.initials: RP
authors.lastname: Moreira
authors.affiliation: Nephrology Division, Department of Medicine, Federal University of São Paulo, Rua Botucatu 740, Vila Clementino, 04023-900 São Paulo, SP, Brazil.
authors.forename: Danielle Yuri
authors.initials: DY
authors.lastname: Arita
authors.affiliation: Nephrology Division, Department of Medicine, Federal University of São Paulo, Rua Botucatu 740, Vila Clementino, 04023-900 São Paulo, SP, Brazil.
authors.forename: Danielle S
authors.initials: DS
authors.lastname: Aragão
authors.affiliation: Nephrology Division, Department of Medicine, Federal University of São Paulo, Rua Botucatu 740, Vila Clementino, 04023-900 São Paulo, SP, Brazil.
authors.forename: Ingrid Kazue Mizuno
authors.initials: IK
authors.lastname: Watanabe
authors.affiliation: Nephrology Division, Department of Medicine, Federal University of São Paulo, Rua Botucatu 740, Vila Clementino, 04023-900 São Paulo, SP, Brazil.
authors.forename: Patricia S
authors.initials: PS
authors.lastname: Dantas
authors.affiliation: Nephrology Division, Department of Medicine, Federal University of São Paulo, Rua Botucatu 740, Vila Clementino, 04023-900 São Paulo, SP, Brazil.
authors.forename: Ralmony
authors.initials: R
authors.lastname: Santos
authors.affiliation: Nephrology Division, Department of Medicine, Federal University of São Paulo, Rua Botucatu 740, Vila Clementino, 04023-900 São Paulo, SP, Brazil.
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Mattar-Rosa
authors.affiliation: Nephrology Division, Department of Medicine, Federal University of São Paulo, Rua Botucatu 740, Vila Clementino, 04023-900 São Paulo, SP, Brazil.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Yokota
authors.affiliation: Science and Technology Department, Federal University of São Paulo, São José dos Campos, SP, Brazil.
authors.forename: Tatiana Sousa
authors.initials: TS
authors.lastname: Cunha
authors.affiliation: Nephrology Division, Department of Medicine, Federal University of São Paulo, Rua Botucatu 740, Vila Clementino, 04023-900 São Paulo, SP, Brazil.
authors.forename: Dulce Elena
authors.initials: DE
authors.lastname: Casarini
mesh_terms: D000803:Angiotensin I / Q000378:metabolism*; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight; D001920:Bradykinin / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000150:complications; D003928:Diabetic Nephropathies / Q000235:genetics* / Q000378:metabolism; D018628:Gene Dosage; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D005838:Genotype; D007668:Kidney / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010446:Peptide Fragments / Q000378:metabolism*; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D012084:Renin-Angiotensin System / Q000187:drug effects; D013050:Spectrometry, Fluorescence
chemical_list: D001786:Blood Glucose; D010446:Peptide Fragments; D000803:Angiotensin I; D007703:Peptidyl-Dipeptidase A; C118790:angiotensin I (1-7); D001920:Bradykinin