Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/102549
Title: NADPH oxidase 4 attenuates cerebral artery changes during the progression of Marfan syndrome
Author: Onetti, Yara
Meirelles, Thayna
Dantas, AnaP.
Schröder, Katrin
Vila, Elisabet
Egea Guri, Gustavo
Jiménez-Altayó, Francesc
Keywords: Teixit connectiu
Malalties hereditàries
Aneurismes aòrtics
Factors de creixement
Connective tissue
Genetic diseases
Aortic aneurysms
Growth factors
Issue Date: 4-Mar-2016
Publisher: American Physiological Society
Abstract: Marfan syndrome (MFS) is a connective tissue disorder that is often associated with the fibrillin-1 (Fbn1) gene mutation and characterized by cardiovascular alterations, predominantly ascending aortic aneurysms. Although neurovascular complications are uncommon in MFS, the improvement in Marfan patients' life expectancy is revealing other secondary alterations, potentially including neurovascular disorders. However, little is known about small-vessel pathophysiology in MFS. MFS is associated with hyperactivated transforming growth factor (TGF)-β signaling, which among numerous other downstream effectors, induces the NADPH oxidase 4 (Nox4) isoform of NADPH oxidase, a strong enzymatic source of H2O2 We hypothesized that MFS induces middle cerebral artery (MCA) alterations and that Nox4 contributes to them. MCA properties from 3-, 6-, or 9-mo-old Marfan (Fbn1(C1039G/+)) mice were compared with those from age/sex-matched wild-type littermates. At 6 mo, Marfan compared with wild-type mice developed higher MCA wall/lumen (wild-type: 0.081 ± 0.004; Marfan: 0.093 ± 0.002; 60 mmHg; P < 0.05), coupled with increased reactive oxygen species production, TGF-β, and Nox4 expression. However, wall stiffness and myogenic autoregulation did not change. To investigate the influence of Nox4 on cerebrovascular properties, we generated Marfan mice with Nox4 deficiency (Nox4(-/-)). Strikingly, Nox4 deletion in Marfan mice aggravated MCA wall thickening (cross-sectional area; Marfan: 6,660 ± 363 μm(2); Marfan Nox4(-/-): 8,795 ± 824 μm(2); 60 mmHg; P < 0.05), accompanied by decreased TGF-β expression and increased collagen deposition and Nox1 expression. These findings provide the first evidence that Nox4 mitigates cerebral artery structural changes in a murine model of MFS.
Note: http://dx.doi.org/10.1152/ajpheart.00770.2015
It is part of: American Journal of Physiology-Heart and Circulatory Physiology, 2016, vol. 310, num. 9, p. H1081-H1090
Related resource: http://dx.doi.org/10.1152/ajpheart.00770.2015
URI: http://hdl.handle.net/2445/102549
ISSN: 0363-6135
Appears in Collections:Articles publicats en revistes (Biomedicina)
Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)

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