Endothelial dysfunction, oxidized lipoproteins and nitric oxide in hypercholesterolemia
Data
2002-06-01
Autores
Ajzen, Sergio Aron 
Abdalla, Dulcineia Saes Parra
Tipo
Artigo
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Resumo
Endothelial dysfunction plays an important role in the pathogenesis of coronary artery disease. Plasma cholesterol, particularly that associated to LDL, has been suggested to be an important risk factor in the development of cardiovascular diseases. Moreover, LDL oxidation is a crucial event in the pathogenesis of atherosclerosis, By the other hand, a reduced bioactivity of endothelial nitric oxide ((.)NO) has been implicated in the pathogenesis of atherosclerosis. The reduction of (.)NO activity in hypercholesterolemia and in other metabolic disorders associated with atherogenesis appears to be multifactorial, However, the alterations of (.)NO production in hypercholesterolemia is still controversial. The purpose of this study was to examine the relationship of lipid peroxidation, antioxidants and nitric oxide bioavailability with the impairment of endothelium dependent vasodilation in hypercholesterolemic (HC) (n = 18) and normolipidemic subjects (N) (n = 11). Ascorbate, urate, a-tocopherol, lycopene and beta-carotene, as well as, lipid hydroxyl hydroperoxides were determined by HPLC. Endothelin was determined by ELISA. The kinetics of LDL oxidation was monitored by incubating LDL with Cu(2+). Oxysterols were determined by GC. Mode B ultrasonography was used to measure the blood flow and diameter in response to reactive hyperemia of brachial artery. The concentrations of nitrate and S-nitrosothiols in blood plasma were determined by chemiluminescence elicited by reaction of (.)NO with ozone in the (.)NO analyzer (NOA(TM280), Sievers, Corp,), The content of nitrotyrosine of blood plasma and LDL was determined by a new chemiluminescence competitive ELISA developed in our laboratory with a polyclonal antibody, Plasma ascorbate, lipid soluble antioxidants, the resistance of LDL to oxidation (lag time) and the endothelium dependent vasorelaxation were lower in HC than in N. Lidid hydroxy / hydroperoxides, endothelin, nitrate, S- nitrosothiols, total cholesterol, apo B, LDL-nitrotyrosine and LDL-cholesterol were significantly higher in HC than in N subjects. LDL cholesterol was negatively correlated to the percentage of diameter increase in response to hyperemia, The concentration of lipid soluble antioxidants was inversely related to the impairment of endothelial dependent vasodilation, In conclusion, the high level of oxidized lipids and endothelin, associated to a decrease of antioxidants and (.)NO bioavailability, can play a role in the impairment of endothelial function, which is crucial to the development of atherosclerosis in hypercholesterolemic patients.
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Citação
Acta Bioquimica Clinica Latinoamericana. La Plata, Buenos Aires: Federacion Bioquimica Provincia Buenos Aires, v. 36, n. 2, p. 243-258, 2002.