Individuals with cystic fibrosis do not display impaired endothelial function or evidence of oxidative damage in endothelial cells exposed to serum

Heightened systemic oxidative stress is increasingly recognized as a featur e of cystic fibrosis (CF). The consequences of long-term exposure to free r adical attack include a predisposition to diseases such as cancer and ather osclerosis. An increased incidence of malignancy among adult patients with CF has been reported, but the absence of atherosclerotic disease is well de scribed. The aim of the present study was to assess endothelial function in vivo and relate this to the potential of serum from patients with CF to in duce oxidative-mediated damage in cultured human endothelial cells. A group of I I CF patients was matched with a group of healthy volunteers with reg ard to age and sex. Endothelial function was assessed as endothelium-depend ent and -independent vasodilation by measuring forearm blood flow in respon se to infused acetylcholine and sodium nitroprusside respectively. Confluen t monolayers of cultured human endothelial cells were exposed to serum from CF patients and control subjects. Following exposure, cell death was asses sed by lactate dehydrogenase release, and the degree of lipid peroxidation in the membrane was assessed by measuring the content of lipid hydroperoxid es, malondialdehyde and 4-hydroxynonenal. Endothelial monolayers exposed to serum from CF patients released significantly less lactate dehydrogenase f ollowing exposure than those exposed to serum from healthy controls (1.8% a nd 3.0% respectively; mean difference - 1.2%; 95% confidence intervals -1.9 % to -0.1 %; P < 0.05) and contained significantly less 4-hydroxynonenal (0 .75 and 3.41 mu mol/g of protein respectively; mean difference -2.66 mu mol /g; 95% confidence intervals -5.10 to -0.22 mu mol/g; P < 0.05). There was no significant difference between patients and controls in the extent of se rum-induced membrane peroxidation, as assessed by malondialdehyde or lipid hydroperoxides, or in endothelial function, as assessed by forearm blood fl ow. In conclusion, despite evidence for heightened systemic oxidative stres s in CF, patients displayed no impairment of endothelial function, and thei r serum caused significantly less damage to human endothelial cells than th at from matched controls.