Microsomal prostaglandin E synthase-1 is involved in the metabolic and cardiovascular alterations associated with obesity
Por:
Ballesteros-Martinez, C, Rodrigues-Diez, R, Beltran, LM, Moreno-Carriles, R, Martinez-Martinez, E, Gonzalez-Amor, M, Martinez-Gonzalez, J, Rodriguez, C, Cachofeiro, V, Salaices, M, Briones, AM
Publicada:
1 jun 2022
Ahead of Print:
1 feb 2022
Resumen:
Background and Purpose Microsomal prostaglandin E synthase-1 (mPGES-1) is an inducible isomerase responsible for prostaglandin E-2 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.
Filiaciones:
Ballesteros-Martinez, C:
Univ Autonoma Madrid, Inst Invest Hosp Univ La Paz IdiPaz, Fac Med, Dept Farmacol, Madrid, Spain
Rodrigues-Diez, R:
Univ Autonoma Madrid, Inst Invest Hosp Univ La Paz IdiPaz, Fac Med, Dept Farmacol, Madrid, Spain
ISCIII, CIBER Enfermedades Cardiovasc, Madrid, Spain
Beltran, LM:
Hosp Univ La Paz, Serv Med Interna, IdiPaz, Madrid, Spain
Univ Seville, Hosp Virgen del Rocio IBiS Sevilla, Dept Med, Serv Med Interna, Seville, Spain
Moreno-Carriles, R:
Hosp Univ La Princesa, Serv Angiol & Cirugia Vasc, Madrid, Spain
Martinez-Martinez, E:
Univ Complutense Madrid, Fac Med, Inst Invest Sanitaria Gregorio Maranon IiSGM, Dept Fisiol, Madrid, Spain
Gonzalez-Amor, M:
Univ Autonoma Madrid, Inst Invest Hosp Univ La Paz IdiPaz, Fac Med, Dept Farmacol, Madrid, Spain
ISCIII, CIBER Enfermedades Cardiovasc, Madrid, Spain
Martinez-Gonzalez, J:
ISCIII, CIBER Enfermedades Cardiovasc, Madrid, Spain
CSIC, Inst Invest Biomed IIB St Pau, Inst Invest Biomed Barcelona IIBB, Barcelona, Spain
Rodriguez, C:
ISCIII, CIBER Enfermedades Cardiovasc, Madrid, Spain
IIB St Pau, Inst Recerca Hosp Santa Creu & St Pau IRHSCSP, Barcelona, Spain
Cachofeiro, V:
ISCIII, CIBER Enfermedades Cardiovasc, Madrid, Spain
Univ Complutense Madrid, Fac Med, Inst Invest Sanitaria Gregorio Maranon IiSGM, Dept Fisiol, Madrid, Spain
Salaices, M:
Univ Autonoma Madrid, Inst Invest Hosp Univ La Paz IdiPaz, Fac Med, Dept Farmacol, Madrid, Spain
ISCIII, CIBER Enfermedades Cardiovasc, Madrid, Spain
Briones, AM:
Univ Autonoma Madrid, Inst Invest Hosp Univ La Paz IdiPaz, Fac Med, Dept Farmacol, Madrid, Spain
ISCIII, CIBER Enfermedades Cardiovasc, Madrid, Spain
hybrid, All Open Access; Green
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