Adipocyte-Specific Mineralocorticoid Receptor Overexpression in Mice Is Associated With Metabolic Syndrome and Vascular Dysfunction: Role of Redox-Sensitive PKG-1 and Rho Kinase

Aurelie Nguyen Dinh Cat, Tayze T. Antunes, Glaucia E. Callera, Ana Sanchez, Sofia Tsiropoulou, Maria G. Dulak-Lis, Aikaterini Anagnostopoulou, Ying He, Augusto C. Montezano, Frederic Jaisser and Rhian M. Touyz 2016. Adipocyte-Specific Mineralocorticoid Receptor Overexpression in Mice Is Associated With Metabolic Syndrome and Vascular Dysfunction: Role of Redox-Sensitive PKG-1 and Rho Kinase. Diabetes. 65 (8), pp. 2392-2403. https://doi.org/10.2337/db15-1627

TitleAdipocyte-Specific Mineralocorticoid Receptor Overexpression in Mice Is Associated With Metabolic Syndrome and Vascular Dysfunction: Role of Redox-Sensitive PKG-1 and Rho Kinase
TypeJournal article
AuthorsAurelie Nguyen Dinh Cat, Tayze T. Antunes, Glaucia E. Callera, Ana Sanchez, Sofia Tsiropoulou, Maria G. Dulak-Lis, Aikaterini Anagnostopoulou, Ying He, Augusto C. Montezano, Frederic Jaisser and Rhian M. Touyz
Abstract

<jats:p>Mineralocorticoid receptor (MR) expression is increased in adipose tissue from obese individuals and animals. We previously demonstrated that adipocyte-MR overexpression (Adipo-MROE) in mice is associated with metabolic changes. Whether adipocyte MR directly influences vascular function in these mice is unknown. We tested this hypothesis in resistant mesenteric arteries from Adipo-MROE mice using myography and in cultured adipocytes. Molecular mechanisms were probed in vessels/vascular smooth muscle cells and adipose tissue/adipocytes and focused on redox-sensitive pathways, Rho kinase activity, and protein kinase G type-1 (PKG-1) signaling. Adipo-MROE versus control-MR mice exhibited reduced vascular contractility, associated with increased generation of adipocyte-derived hydrogen peroxide, activation of vascular redox-sensitive PKG-1, and downregulation of Rho kinase activity. Associated with these vascular changes was increased elastin content in Adipo-MROE. Inhibition of PKG-1 with Rp-8-Br-PET-cGMPS normalized vascular contractility in Adipo-MROE. In the presence of adipocyte-conditioned culture medium, anticontractile effects of the adipose tissue were lost in Adipo-MROE mice but not in control-MR mice. In conclusion, adipocyte-MR upregulation leads to impaired contractility with preserved endothelial function and normal blood pressure. Increased elasticity may contribute to hypocontractility. We also identify functional cross talk between adipocyte MR and arteries and describe novel mechanisms involving redox-sensitive PKG-1 and Rho kinase. Our results suggest that adipose tissue from Adipo-MROE secrete vasoactive factors that preferentially influence vascular smooth muscle cells rather than endothelial cells. Our findings may be important in obesity/adiposity where adipocyte-MR expression/signaling is amplified and vascular risk increased.</jats:p>

JournalDiabetes
Journal citation65 (8), pp. 2392-2403
ISSN0012-1797
1939-327X
Year2016
PublisherAmerican Diabetes Association
Digital Object Identifier (DOI)https://doi.org/10.2337/db15-1627
Web address (URL)http://dx.doi.org/10.2337/db15-1627
Publication dates
Published19 Aug 2016

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