Biography

Biography: Abeer M. Mahmoud

Abstract

Obesity-associated Hypoxia Contributes to Aberrant Methylation of Genes Implicated in Inflammation and vascular Function

Abeer M. Mahmoud

University of Illinois, USA

Abstract

Introduction: Obesity is a major risk factor for cardiovascular disease. We previously demonstrated an impaired vascular function in obese adults (OB). We now hypothesize a role of obesity-associated hypoxia in disturbing the methylation/expression of genes involved in inflammation/vascular function. We also propose a mediating role of the hypoxia-inducible factor, HIF1α and the DNA hydroxymethylase, TET1.

Methods: We obtained subcutaneous and visceral adipose tissue (AT) biopsies from bariatric patients (n=60; age: 36±7 yrs; BMI: 50.7±8.7 kg/m2) and non-obese (NOB) adults having elective surgeries (n=30; age: 36±2 yrs; BMI: 25.8±1 kg/m2). AT-isolated arterioles were tested for vasoreactivity in response to pressure gradients of ∆10-∆100 cmH₂O. Arteriolar nitric oxide (NO) and reactive oxygen species (ROS) were measured. Protein expression of HIF1α and TET1 and methylation/expression of leptin, IL1β, IL6, IL8, IL17, CXCL5, TNF-α, and IFNÉ£ were measured in the AT.

Results: Flow-induced dilation (FID) was 40-50% higher in NOB than OB adults across all pressure gradients (p<0.05). NO production was higher, and ROS generation was lower in OB arterioles compared to NOB. HIF1α and TET1 proteins were 2-4-fold higher in OB compared to NOB adults and correlated negatively with arteriolar FID, NO, and brachial artery FID (r=0.82, 0.64, 0.91, respectively; p<0.001) and positively with ROS (r=-0.71, p<0.01). Global hydroxymethylation and adipocytokine promoter hypomethylation and increased expression were observed in OB compared to NOB.

Conclusion: Our results suggest that vascular dysfunction in OB adults may be attributed to aberrant DNA methylation and increased expression of adipocytokines. This conclusion was also supported by invitro mechanistic studies.

Biography

Abeer Mahmoud has received her MD degree and residency training as a Pathologist from Assiut University, Egypt. She served as a surgical/clinical pathologist at South Egypt Cancer Institute (2002-2008). She earned her Ph.D. in Pathology (College of Medicine, the University of Illinois at Chicago, 2013) and received postdoctoral training in physiological and molecular outcomes of lifestyle interventions at the metabolic and vascular levels. She is currently an Assistant Professor in the Department of Medicine at UIC and funded by the NIH/NHLBI to study DNA methylation profiles among morbidly obese and the impact on metabolic and vascular functions.

                                                                                                                          amahmo4@uic.edu