Study of endothelial dysfunction and vascular inflammation in sleep apnea, obesity and aged humans

Obstructive sleep apnea [OSA] has been associated with cardiovascular complications. The overnight repetitive hypoxia represents a form of oxidative stress in the vasculature which may activate the oxidant-sensitive, proinflammatory transcription factor nuclear factor kjB [NF-kjB], affecting endothelial function and atherosclerosis. We investigated whether the endothelial alterations attributed to OSA rather than to other confounding factors. Also, the production of inflammatory cytokine nuclear factor-kappa beta [NFKbeta] was investigated as the molecular mechanism involved in vascular endothelial dysfunction with OSA. Sixty subjects underwent attended nocturnal polysomnography were grouped by apnea hypopnea index: control [AHI<5/h] and OSA cases [AHI>5/h] the cases were further classified according to age and BMI into subgroup IIA: OSA, non-obese, middle age [35-52 y], subgroup IIB: OSA, non-obese, older age group [55-68 y], subgroup IIIA: OSA, obese, middle age group [35-52 y] and subgroup IIIB: OSA, obese, older age group [55-68 y]. A morning venous blood sample was obtained. Neutrophils were isolated, and NF-kjB activity was determined. Plasma sVCAM-1 was assayed by enzyme-linked immunosorbent assay and flow-mediated dilation [FMD] was performed. NF-jB activation and plasma level of sVCAM-1 were significantly increased in OSA patients as compared to the control group and there was no significant difference between the obese and non-obese cases also no significant difference between the middle and old age cases. The degree of NF-kjB activation was positively correlated with indices of apnea severity[r = 0.938; p< 0.001]. FMD was significantly decreased in OSA patients as compared to the control group. These findings suggested that OSA is an independent risk factor for cardiovascular morbidity also that OSA leads to NF-kjB activation, which may constitute an important pathway linking OSA with systemic inflammation and cardiovascular disease

pathogenic role of homocysteinemia in experimental uraemia: effect on endothelial function, lipid profile and role of vitamin therapy

Objective: evaluating the elevation of homocysteine in experimental uraemia and its effect on vascular endothelial cell function, chronic inflammation, and lipid profile, while testing if any of these effects can be reversed by administration of the vitamins involved in homocysteine degradation

Methods: this work included 60 adult male Wistar rats divided equally into 4 groups; control, placebo. B12 and folic acid and B6-treated groups. Groups II, III and IV were subjected to chronic renal failure produced by right nephrectomy together with subtotal excision of the left kidney. Control rats were Sham-operated by flank incisions. Vitamin and placebo therapy were delivered orally by gastric tube. All therapies were started 3 weeks after induction of uremia. In all four groups, the following parameters were assessed three weeks after induction of uremia, and re-assessed in groups II, III and IV after the six weeks of vitamin or placebo therapy:- plasma total homocysteine, plasma von Willibrand factor. C-reactive protein and serum lipid profile

Results: hyperhomocysteinemia was found in groups II, III and IV when compared to control group. A significant decline of plasma total homocysteine was found in group III [treated with B12 and folic acid] when compared to pre-treatment values. Meanwhile, B6 administration did not result in any significant difference between pre-and post-treatment values. Reduction of plasma triglyceride levels was observed in group Ill and in group IV. Moreover, total plasma cholesterol levels were also significantly reduced in the post-treated groups [III and IV] when compared to its pre-treatment values. Although both folic acid and vit B12 were as highly effective as vit B6 in decreasing triglyceride and cholesterol levels, only folic acid and vit B12 have resulted in a marked improvement in total homocysteine levels. Also, folic acid and vitamin B12 administration resulted in a significant decrease in vWF when compared to pretreatment values. CRP was significantly elevated in the uremic groups when compared to the control group. Moreover, a significant positive correlation was found between plasma total hornocysteine and CRP, also between CRP and vWF in all the studied groups

Conclusion: 1. Elevated plasma total homocysteine levels, CRP, Cholesterol, triglyceriodes and vWF in uremic rats are potential risk factors for atherosclerotic vascular disease. 2. Hyperhomocysteinemia and lipid profile disturbances in chronic renal failure could be ameliorated by supplementation of folic acid, B12 and pyridoxine for a long period of time