Microsomal prostaglandin E synthase-1 is involved in the metabolic and cardiovascular alterations associated with obesity
Ballesteros-Martínez, Constanza (Instituto de Investigación Sanitaria del Hospital Universitario La Paz)
Rodrigues-Díez, Raquel (CIBER de Enfermedades Cardiovasculares. ISCIII)
Beltrán, Luis M. (Instituto de Biomedicina de Sevilla)
Moreno-Carriles, Rosa (Hospital Universitario de la Princesa (Madrid))
Martínez-Martínez, Ernesto (Universidad Complutense de Madrid. Departamento de Fisiología)
González-Amor, María (CIBER de Enfermedades Cardiovasculares. ISCIII)
Martínez-González, José (Institut d'Investigació Biomèdica Sant Pau)
Rodríguez, Cristina (Institut d'Investigació Biomèdica Sant Pau)
Cachofeiro, Victoria (Universidad Complutense de Madrid. Departamento de Fisiología)
Salaices, Mercedes (CIBER de Enfermedades Cardiovasculares. ISCIII)
Briones, Ana M. (CIBER de Enfermedades Cardiovasculares. ISCIII)

Data:	2022
Resum:	Background and Purpose: Microsomal prostaglandin E synthase-1 (mPGES-1) is an inducible isomerase responsible for prostaglandin E production in inflammatory conditions. We evaluated the role of mPGES-1 in the development and the metabolic and cardiovascular alterations of obesity. Experimental Approach: mPGES-1 and mPGES-1 mice were fed with normal or high fat diet (HFD, 60% fat). The glycaemic and lipid profile was evaluated by glucose and insulin tolerance tests and colorimetric assays. Vascular function, structure and mechanics were assessed 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 was correlated with vascular damage. Key Results: 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 with mPGES-1 mice. mPGES-1 knockdown prevented cardiomyocyte hypertrophy, cardiac fibrosis, endothelial dysfunction, aortic insulin resistance, and vascular inflammation and remodelling, 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 remodelling, vessel stiffness, and systolic blood pressure. In human PVAT, there was a positive correlation between mPGES-1 expression and inflammatory markers. Conclusions and Implications: mPGES-1 inhibition might be a novel therapeutic approach to the management of obesity and the associated cardiovascular and metabolic alterations.
Ajuts:	Ministerio de Ciencia e Innovación SAF2016-80305P Instituto de Salud Carlos III FIS PI18/0257 Agencia Estatal de Investigación IJCI-2017-31399
Nota:	Altres ajuts: Fondo Europeo de Desarrollo Regional (FEDER); Comunidad de Madrid (CM B2017/BMD-3676 AORTASANA).
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Adipose tissue alterations ; Inflammation ; Mpges-1 ; Obesity ; Vascular function and remodelling
Publicat a:	British Journal of Pharmacology, Vol. 179 Núm. 11 (june 2022) , p. 2733-2753, ISSN 1476-5381

DOI: 10.1111/bph.15776
PMID: 34877656

21 p, 33.2 MB

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