Artículo
Hypertension secondary to nitric oxide depletion produces oxidative imbalance and inflammatory/fibrotic outcomes in the cornea of C57BL/6 mice.
Autor/es | Santana Garrido, Álvaro
Reyes Goya, Claudia Arroyo Barrios, Ana María Andre, Helder Vázquez Cueto, Carmen María Mate Barrero, Alfonso |
Departamento | Universidad de Sevilla. Departamento de Fisiología |
Fecha de publicación | 2022 |
Fecha de depósito | 2023-06-01 |
Publicado en |
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Resumen | Arterial hypertension (AH) leads to oxidative and infammatory imbalance that contribute to fbrosis development in many
target organs. Here, we aimed to highlight the harmful efects of severe AH in the cornea. Our experimental ... Arterial hypertension (AH) leads to oxidative and infammatory imbalance that contribute to fbrosis development in many target organs. Here, we aimed to highlight the harmful efects of severe AH in the cornea. Our experimental model was established by administration of NG-nitro-L-arginine-methyl-ester (L-NAME) to C57BL/6 mice, which were monitored weekly for arterial blood pressure and intraocular pressure (IOP). Morphological studies of ocular tissues were accompanied by analyses of reactive oxygen species generation, and localization/expression of NAPDH oxidase isoforms (NOX1, NOX2, NOX4) and infammatory biomarkers (PPARα, PPARγ, IL-1β, IL-6, IL-10, TNF-α, and COX-2). Masson’s trichrome and Sirius Red staining were used to explore the fbrotic status of the cornea. The expression of collagen isoforms (COL1α1, COL1α2, COL3α1, COL4α1, COL4α2) and relevant metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) were also quantifed to evaluate the participation of collagen metabolism in AH-related corneal damage. Hypertensive animals showed an increase in IOP values, and a thinner cornea compared with normotensive controls. Moreover, AH increased NADPH oxidase activity and reactive oxygen species generation in the cornea, which was accompanied by transcriptional upregulation of NOX isoforms and infammatory biomarkers, while reducing PPAR expression. L-NAME-treated animals also developed corneal fbrosis with overexpression of collagen isoforms and reduction of factors responsible for collagen degradation. This is the frst study reporting structural changes in the cornea and elevated IOP in L-NAME-treated mice. Overexpression of the NADPH oxidase system and collagen deposition might play a substantial role in the pathogenic mechanisms contributing to ocular disturbances in a context of severe hypertension. |
Agencias financiadoras | Ministerio de Ciencia e Innovación (MICIN). España Agencia Estatal de Investigación. España Universidad de Sevilla |
Identificador del proyecto | PID2019-109002RB-I00
2020/275 2021/188 CTS-584 USE VI PPIT |
Cita | Santana Garrido, Á., Reyes Goya, C., Arroyo Barrios, A.M., Andre, H., Vázquez Cueto, C.M. y Mate Barrero, A. (2022). Hypertension secondary to nitric oxide depletion produces oxidative imbalance and inflammatory/fibrotic outcomes in the cornea of C57BL/6 mice.. Journal of Physiology and Biochemistry, 78 (4), 915-932. https://doi.org/10.1007/s13105-022-00916-2. |
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s13105-022-00916-2.pdf | 4.357Mb | [PDF] | Ver/ | |