Dataset Information

Preservation of vascular endothelial repair in mice with diet-induced obesity.

ABSTRACT:

Introduction

Preservation of structural integrity of the endothelial monolayer and maintenance of endothelial cell function are of critical importance in preventing arterial thrombosis, restenosis and atherosclerosis. Obesity has been intimately linked with endothelial dysfunction, and reports of reduced abundance and functional impairment of circulating progenitor cells in obesity have led to the suggestion that defective endothelial repair contributes to obesity-related cardiovascular disease.

Methods

C57BL/6 mice were fed a high-fat diet for either 3 or 6 months to induce obesity; metabolic phenotyping was then carried out before femoral artery wire injury was performed. Endothelial regeneration was then quantified. Mononuclear cells and myeloid angiogenic cells were cultured and characterized for pro-angiogenic properties.

Results

No impairment of endothelial regeneration following mechanical endothelial injury in diet-induced obese mice when compared with chow-fed controls was observed, despite the induction of an adverse metabolic phenotype characterized by glucose intolerance and insulin resistance. Dietary-obese mice had increased numbers of circulating myeloid angiogenic cells, which retained normal functional properties including intact paracrine angiogenic effects.

Conclusion

Preserved endothelial regeneration despite metabolic dysregulation in dietary obese mice suggests that compensatory mechanisms mitigate the deleterious influence of insulin resistance on endothelial repair in obesity.

SUBMITTER: Rashid ST

PROVIDER: S-EPMC6180714 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Preservation of vascular endothelial repair in mice with diet-induced obesity.

Rashid S T ST Haywood N J NJ Yuldasheva N Y NY Smith J J Aziz A A Scott D J A DJA Kearney M T MT Wheatcroft S B SB

Obesity science & practice 20180626 5

<h4>Introduction</h4>Preservation of structural integrity of the endothelial monolayer and maintenance of endothelial cell function are of critical importance in preventing arterial thrombosis, restenosis and atherosclerosis. Obesity has been intimately linked with endothelial dysfunction, and reports of reduced abundance and functional impairment of circulating progenitor cells in obesity have led to the suggestion that defective endothelial repair contributes to obesity-related cardiovascular ...[more]

PMID: 30338120

Similar Datasets

Project description:Obesity, where there is enhancement of stored body fat in adipose tissues, is associated with cardiovascular complications that are mainly related to atherosclerosis. Time-restricted feeding (TRF) is a form of restricted eating aimed at reducing weight in obese subjects. The present study aims to investigate changes in vascular endothelial function, endothelial nitric oxide synthase (eNOS), and protein kinase B (Akt) protein expressions with TRF in obese and normal rats. Male Sprague Dawley rats were divided into two normal and three obese groups; obesity was induced in the obese groups by feeding with a high-fat diet (HFD) for six weeks. After six weeks, rats were equally divided into five groups (n = 7 per group): Normal group (NR) which continued on a standard diet for six more weeks, normal group switched to TRF with a standard diet for six weeks (NR + TRFSD), obese group (OR) which continued on HFD for six more weeks, obese group switched to TRF of HFD (OR + TRFHFD), and obese group switched to TRF of a standard diet (OR + TRFSD). TRF was practiced for six weeks, after which the rats were sacrificed. Aortic endothelium-dependent and endothelium-independent relaxations and contractions were assessed using the organ bath. Aortic eNOS and Akt protein expressions were determined using immunoblotting. Fasting blood glucose, body weight, body mass index (BMI), serum lipid profile, Lee's index, serum insulin levels, and sensitivity (HOMA-IR) were also measured. Endothelium-dependent relaxation was significantly impaired, while endothelium-dependent contraction increased in obese rats compared to that in normal rats. Both obese groups which underwent TRF with a HFD and standard diet improved their impairments in endothelium-dependent relaxation and reduced endothelium-dependent contraction; these were associated with increased expressions of aortic eNOS and Akt protein. Both obese groups with TRF reduced body weight, BMI, Lee's index, total cholesterol, triglycerides, low-density lipoprotein cholesterol, and improved insulin sensitivity. TRF improved endothelium-dependent relaxation and reduced endothelium-dependent contraction, thus attenuating endothelial dysfunction in obese rats. These were associated with increased aortic eNOS and Akt protein expressions.

Project description:AimsAldosterone plays a crucial role in cardiovascular disease. 'Systemic' inhibition of its mineralocorticoid receptor (MR) decreases atherosclerosis by reducing inflammation and oxidative stress. Obesity, an important cardiovascular risk factor, is an inflammatory disease associated with increased plasma aldosterone levels. We have investigated the role of the 'endothelial' MR in obesity-induced endothelial dysfunction, the earliest stage in atherogenesis.Methods and resultsC57BL/6 mice were exposed to a normal chow diet (ND) or a high-fat diet (HFD) alone or in combination with the MR antagonist eplerenone (200 mg/kg/day) for 14 weeks. Diet-induced obesity impaired endothelium-dependent relaxation in response to acetylcholine, whereas eplerenone treatment of obese mice prevented this. Expression analyses in aortic endothelial cells isolated from these mice revealed that eplerenone attenuated expression of pro-oxidative NADPH oxidase (subunits p22phox, p40phox) and increased expression of antioxidative genes (glutathione peroxidase-1, superoxide dismutase-1 and -3) in obesity. Eplerenone did not affect obesity-induced upregulation of cyclooxygenase (COX)-1 or prostacyclin synthase. Endothelial-specific MR deletion prevented endothelial dysfunction in obese (exhibiting high 'endogenous' aldosterone) and in 'exogenous' aldosterone-infused lean mice. Pre-incubation of aortic rings from aldosterone-treated animals with the COX-inhibitor indomethacin restored endothelial function. Exogenous aldosterone administration induced endothelial expression of p22phox in the presence, but not in the absence of the endothelial MR.ConclusionObesity-induced endothelial dysfunction depends on the 'endothelial' MR and is mediated by an imbalance of oxidative stress-modulating mechanisms. Therefore, MR antagonists may represent an attractive therapeutic strategy in the increasing population of obese patients to decrease vascular dysfunction and subsequent atherosclerotic complications.

Dataset Information

Preservation of vascular endothelial repair in mice with diet-induced obesity.

Introduction

Methods

Results

Conclusion

Publications

Preservation of vascular endothelial repair in mice with diet-induced obesity.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets