Microsomal prostaglandin E synthase‐1 is involved in the metabolic and cardiovascular alterations associated with obesity

Abstract

Background and Purpose 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. 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.

Arterial Stiffness Assessment by Pulse Wave Velocity in Patients with Metabolic Syndrome and Its Components: Is It a Useful Tool in Clinical Practice?

“…In addition, brachial–ankle PWV values after weight regaining were independent of body weight, high-sensitivity C-reactive protein (hs-CRP), or insulin resistance changes [ 56 ]. However, it is still unknown what impacts a decrease in PWV value after weight reduction the most; whether it depends on changes in adipokines and inflammatory markers or is due to weight reduction per se [ 57 , 58 ].…”

The Synthetic Flavonoid Hidrosmin Improves Endothelial Dysfunction and Atherosclerotic Lesions in Diabetic Mice

“…After dissection, vessels were mounted in an isometric myograph (Danish Myo Tech, Aarhus, Denmark). After an equilibration period for 30 min at 37 °C in the organ bath, the arterial diameter for optimal tension development was determined as described [ 34 ]. Segment’s viability was then studied by initial exposure to a high-potasium (K + ) solution (120 mmol/L KCl) in KHS (K + -KHS).…”

“…From these images, measurements of internal and external diameters (Di and De) were obtained under passive conditions at each intraluminal pressure using ImageJ software. Structural and mechanical parameters were calculated as described [ 34 ]. Briefly, Cross-sectional area = π/4 × (De 2 − Di 2 ).…”

Emerging roles of interferon-stimulated gene-15 in age-related telomere attrition, the DNA damage response, and cardiovascular disease

“…Human studies have shown a positive correlation between plasma glucose, obesity, and Isg15 mRNA levels in peripheral blood mononuclear cells ( Gonzalez-Amor et al, 2022 ). Moreover, mice fed a high-fat diet (HFD) show increased aortic mRNA expression of Isg15 and other inflammatory genes such as Ccl2 , Il1b , and Tnfa ( Ballesteros-Martinez et al, 2022 ) . Using GEO data base query and related online analytical tools, Sun et al identified ISG15 amongst five genes that were related to both T2M and ovarian cancer, and found that ISG15 expression in ovarian cancer biopsies significantly correlated with patient’s survival time ( Sun et al, 2019 ).…”

“…A recent study of the ISG15 pathway in vascular pathophysiology found that Isg15 expression is increased in the aortas of hypertensive animals and in angiotensin II-treated vascular cells and macrophages (Gonzalez-Amor et al, 2022). The same study found that ISG15 expression in human peripheral blood mononuclear cells positively correlated with systolic and diastolic blood pressure and with carotid intima-media thickness and also found elevated ISG15 expression in human and mouse abdominal aortic aneurysms (Gonzalez-Amor et al, 2022). Moreover, Isg15-null mice were found to be protected against angiotensin II-induced hypertension, elastin remodeling, vascular stiffness, endothelial dysfunction, and expression of inflammatory and oxidative stress markers (Gonzalez-Amor et al, 2022).…”