title: Vasoprotective effects of neurocompensatory response to balloon injury during diabetes involve the improvement of Mas signaling by TGFβ1 activation.
abstract: Balloon injury in diabetic rats triggers a sensory neurocompensatory response that restores the blood flow in contralateral carotid. These vasoprotective effects result from H2O2-mediated relaxation that counteracts AT1-dependent contractile hyperreactivity. The most important mechanism from the renin-angiotensin-system in counteracting AT1-mediated effects is that one is mediated by Mas receptors. Thus, we hypothesized that the vasoprotective effects of balloon neurocompensation in diabetic rats could result from the improvement of Mas signaling by H2O2-mediated sensory mechanisms. NK1 receptors are sensory components whose activation could lead to H2O2 generation upon TGFβ1 release and ALK5-mediated Nox4 upregulation. Based on this, we aimed to investigate: (1) the role of the TGFβ1/ALK5-Nox4-H2O2 pathway on modulating Mas signaling in diabetic rat contralateral carotid; and (2) the contribution of Mas signaling in the control of local blood flow. Our results showed that balloon neurocompensation restored diabetic rat contralateral carotid flow by improving Mas signaling through NK1-mediated TGFβ1 release. TGFβ1/ALK5 activation enhanced Nox4 expression and Nox4-driven generation of H2O2. In turn, H2O2 enhanced the local Mas-mediated relaxation. Since restenosis impairs diabetic rat ipsilateral carotid flow, the restoration of diabetic rat contralateral carotid flow may prevent further damages in cerebral irrigation by carotid pathways after angioplasty during diabetes.
authors.affiliation: Laboratory of Vascular Injury, Department of Physics and Chemistry, Faculty of Pharmaceutical Sciences from Ribeirão Preto (FCFRP), University of São Paulo (USP), Avenida do Café s/n, 14040-903 Ribeirão Preto, SP, Brazil. Electronic address: l.pernomian@usp.br.
authors.forename: Larissa
authors.initials: L
authors.lastname: Pernomian
authors.affiliation: Laboratory of Vascular Injury, Department of Physics and Chemistry, Faculty of Pharmaceutical Sciences from Ribeirão Preto (FCFRP), University of São Paulo (USP), Avenida do Café s/n, 14040-903 Ribeirão Preto, SP, Brazil.
authors.forename: Mayara S
authors.initials: MS
authors.lastname: Gomes
authors.affiliation: Department of Pharmacology, Faculty of Medicine from Ribeirão Preto (FMRP), University of São Paulo (USP), Avenida Bandeirantes, 3900, 14049-900 Ribeirão Preto, SP, Brazil.
authors.forename: Laena
authors.initials: L
authors.lastname: Pernomian
authors.affiliation: Laboratory of Vascular Injury, Department of Physics and Chemistry, Faculty of Pharmaceutical Sciences from Ribeirão Preto (FCFRP), University of São Paulo (USP), Avenida do Café s/n, 14040-903 Ribeirão Preto, SP, Brazil.
authors.forename: Rafael P
authors.initials: RP
authors.lastname: Moreira
authors.affiliation: Department of Pharmacology, Faculty of Medicine from Ribeirão Preto (FMRP), University of São Paulo (USP), Avenida Bandeirantes, 3900, 14049-900 Ribeirão Preto, SP, Brazil.
authors.forename: Fernando M A
authors.initials: FM
authors.lastname: Corrêa
authors.affiliation: Laboratory of Vascular Injury, Department of Physics and Chemistry, Faculty of Pharmaceutical Sciences from Ribeirão Preto (FCFRP), University of São Paulo (USP), Avenida do Café s/n, 14040-903 Ribeirão Preto, SP, Brazil.
authors.forename: Ana M
authors.initials: AM
authors.lastname: de Oliveira
mesh_terms: D000818:Animals; D021721:Balloon Occlusion / Q000009:adverse effects; D020212:Carotid Artery Injuries / Q000378:metabolism* / Q000517:prevention & control*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D008297:Male; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D043562:Receptors, G-Protein-Coupled / Q000096:biosynthesis*; D015398:Signal Transduction / Q000502:physiology*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*; D014664:Vasodilation / Q000502:physiology*
chemical_list: D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D043562:Receptors, G-Protein-Coupled; C508962:Tgfb1 protein, rat; D053773:Transforming Growth Factor beta1
keywords: Angiotensin-(1–7); Carotid balloon injury; Hydrogen peroxide; TGFβ(1); Type I-diabetes