Aziz Momin

Endothelial Function and Weight Loss in Obese Humans

Background: Obesity is a major risk factor for the development of endothelial dysfunction. We explored the effect of different degrees of body mass on endothelial function, lipids, systemic inflammation and glucose homeostasis and the effect of surgically-induced weight loss on endothelial function in severely obese humans. Methods: A cross-sectional study of healthy subjects across a wide range of body fatness was performed to characterize the effect of obesity on flow-mediated dilatation (FMD), systemic inflammation, blood pressure and insulin sensitivity. A longitudinal study was performed to assess the effect of bariatric surgery induced weight loss on these parameters. 73 healthy subjects across a wide range of body mass were recruited; of these, 8 underwent bariatric surgery (median BMI 52.2 kg/m2, interquartile range 50.355.9). Endothelial dependent vasodilatation was measured using the brachial artery vasodilatory response to forearm hyperemia assessed using highresolution ultrasonography. Results: Obese subjects were characterised by a complex collection of abnormalities, with hypertension, impaired glucose homeostasis, systemic inflammation and reduced FMD. BMI ≤25 kg/m2 (median FMD 9.7%, interquartile range 6.8-12.2), BMI >30 kg/m2 (median FMD 6.7% 4.8-7.5), P=0.01 comparing FMD in lean and obese subjects. A mean reduction in weight of 23.4 (4.6) kg produced an improvement in FMD from 5.3% (3.87.0) to 10.2% (7.6-13.3), P=0.01. Conclusions: Even moderate obesity leads to endothelial dysfunction. In severely obese subjects, FMD is normalized by weight loss. This improvement in FMD is associated with a decline in inflammatory markers, blood pressure and insulin. The improvement in FMD occurred despite patients remaining significantly obese. These results suggest that an integrated approach to improving endothelial function in obese humans may be necessary.

Effect of fat distribution on endothelial-dependent and endothelial-independent vasodilatation in healthy humans

Aim:  The present study aims to explore the relationship between inflammatory cytokines, plasma lipids, insulin, blood pressure (BP), total adiposity/markers of fat distribution and endothelial function in healthy people across a wide range of body fatness.

Reduced Nicotinamide Adenine Dinucleotide Phosphate Oxidase-Derived Superoxide and Vascular Endothelial Dysfunction in Human Heart Failure

OBJECTIVES We investigated the role of reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase in endothelial dysfunction in human heart failure. BACKGROUND Vascular endothelial dysfunction in human heart failure contributes to increased tone, exercise limitation, and dysregulation of venous capacitance and vascular volume. The NADPH oxidases (Nox) are an important source of oxidative stress, but their role in the endothelial dysfunction of human heart failure remains unknown. METHODS Endothelium-dependent and -independent vasorelaxation were assessed in saphenous vein segments obtained from consecutive patients with heart failure (n = 19) or normal left ventricular function (control; n = 35) undergoing coronary artery bypass graft. Saphenous vein superoxide production was measured by lucigenin-enhanced chemiluminescence and messenger ribonucleic acid expression of relevant transcripts quantified by real-time polymerase chain reaction. RESULTS Heart failure patients had significantly worse endothelial function than control subjects (15.2 +/- 3% vs. 40.5 +/- 8.4% relative relaxation; p < 0.05), elevated C-reactive protein (CRP) levels (8.6 +/- 2.7 mg/l vs. 2.6 +/- 0.4 mg/l; p < 0.05), over 2-fold higher NADPH-dependent superoxide generation (p < 0.05), and significantly higher expression of the Nox4 isoform and regulatory subunit p67phox. Superoxide levels were positively correlated with New York Heart Association functional class (r = 0.684; p < 0.05) and CRP (r = 0.501; p < 0.005; n = 32). CONCLUSIONS Venous endothelial dysfunction in human heart failure is associated with increased Nox-derived superoxide generation. Inflammatory mechanisms may be involved in the increased reactive oxygen species generation.