Microsomal prostaglandin E synthase-1 (mPGES-1) is involved in the metabolic and cardiovascular alterations associated with obesity
Microsomal prostaglandin E synthase-1 (mPGES-1) is an inducible isomerase responsible for prostaglandin E2 production in inflammatory conditions. We evaluated the role of mPGES-1 in obesity development and in the metabolic and cardiovascular alterations associated.mPGES-1+/+ and mPGES-1-/- mice were...
| Autores: | , , , , , , , , , , |
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| Formato: | artículo |
| Fecha de publicación: | 2021 |
| País: | España |
| Recursos: | Universidad Autónoma de Madrid |
| Repositorio: | Biblos-e Archivo. Repositorio Institucional de la UAM |
| Idioma: | inglés |
| OAI Identifier: | oai:repositorio.uam.es:10486/700685 |
| Acesso em linha: | http://hdl.handle.net/10486/700685 https://dx.doi.org/10.1111/bph.15776 |
| Access Level: | acceso abierto |
| Palavra-chave: | mPGES-1 obesity adipose tissue alterations vascular function and remodeling inflammation Farmacia Medicina |
| Resumo: | Microsomal prostaglandin E synthase-1 (mPGES-1) is an inducible isomerase responsible for prostaglandin E2 production in inflammatory conditions. We evaluated the role of mPGES-1 in obesity development and in the metabolic and cardiovascular alterations associated.mPGES-1+/+ and mPGES-1-/- mice were fed with normal or high fat diet (HFD, 60% fat). The glycaemic and lipid profile was studied by glucose and insulin tolerance tests and colorimetric assays. Vascular function, structure and mechanics were evaluated by myography. Histological studies, q-RT-PCR and Western Blot analyses were performed in adipose tissue depots and cardiovascular tissues. Gene expression in abdominal fat and perivascular adipose tissue (PVAT) from patients and its correlation with vascular damage was determined.Male mPGES-1-/- mice fed with HFD were protected against body weight gain and showed reduced adiposity, better glucose tolerance and insulin sensitivity, lipid levels and less white adipose tissue and PVAT inflammation and fibrosis, compared to mPGES-1+/+ mice. mPGES-1 knockdown prevented cardiomyocyte hypertrophy, cardiac fibrosis, endothelial dysfunction, aortic insulin resistance, and vascular inflammation and remodeling, induced by HFD. Obesity-induced weight gain and endothelial dysfunction of resistance arteries were ameliorated in female mPGES-1-/- mice. In humans, we found a positive correlation between mPGES-1 expression in abdominal fat and vascular remodeling, vessel stiffness and systolic blood pressure. In human PVAT, there was a positive correlation between mPGES-1 expression and inflammatory markers.mPGES-1 inhibition might be a novel therapeutic approach for the management of obesity and the associated cardiovascular and metabolic alterations |
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