RT Journal Article
T1 Microsomal prostaglandin E synthase-1 is involved in the metabolic and cardiovascular alterations associated with obesity.
A1 Ballesteros-Martínez, Constanza
A1 Rodrigues-Díez, Raquel
A1 Beltrán, Luis M
A1 Moreno-Carriles, Rosa
A1 Martínez-Martínez, Ernesto
A1 González-Amor, María
A1 Martínez-González, Jose
A1 Rodríguez, Cristina
A1 Cachofeiro, Victoria
A1 Salaices, Mercedes
A1 Briones, Ana M
K1 adipose tissue alterations
K1 inflammation
K1 mPGES-1
K1 obesity
K1 vascular function and remodelling
AB 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 the development and the metabolic and cardiovascular alterations of obesity. 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. 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. mPGES-1 inhibition might be a novel therapeutic approach to the management of obesity and the associated cardiovascular and metabolic alterations.
YR 2022
FD 2022-02-05
LK http://hdl.handle.net/10668/19921
UL http://hdl.handle.net/10668/19921
LA en
DS RISalud
RD Apr 6, 2025