Glycated high-density lipoprotein regulates reactive oxygen species and reactive nitrogen species in endothelial cells.
ABSTRACT Nonenzymatic glycosylation of plasma proteins may contribute to the excess risk of developing atherosclerosis in patients with diabetes mellitus. Although it is believed that high-density lipoprotein (HDL) is glycosylated at an increased level in diabetic individuals, little is known about a possible linkage between glycated HDL and endothelial dysfunction in diabetes. To clarify whether glucose-modified HDL affects the function of endothelial cells, we first examined herein the level of H(2)O(2) generation from cultured human aortic endothelial cells (HAECs) exposed to a glycated oxidized HDL (gly-ox-HDL) prepared in vitro. Incubation for 48 hours with 100 microg/mL of gly-ox-HDL induced significant release of H(2)O(2) from cells and gly-ox-HDL-induced H(2)O(2) formation was inhibited in the presence of diphenyleneiodonium, an inhibitor of NADPH oxidase. In addition, stimulation of HAECs with gly-ox-HDL for 48 hours elicited a marked downregulation of catalase and Cu(2+), Zn(2+)-superoxide dismutase (CuZn-SOD), suggesting H(2)O(2) formation by gly-ox-HDL to be due to a disturbance involving oxidant and antioxidant enzymes in the cells. Treatment of HAECs with gly-ox-HDL attenuated the expression of endothelial nitric oxide synthase (eNOS), but not inducible nitric oxide synthase (iNOS), and this was followed by decreased production of nitric oxide (NO) by the cells. Furthermore, in vitro experiments with glycated HDL (gly-HDL) in the presence of 2 mmol/L EDTA and Cu(2+)-oxidized HDL suggested the effect of gly-HDL on endothelial function to be possibly potentiated by additional oxidative modification. Taking all of the above findings together, gly-ox-HDL may lead to the deterioration of vascular function through altered production of reactive oxygen species and reactive nitrogen species in endothelial cells.
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ABSTRACT: Summary Dyslipidemia seen in the critically ill patient is a common disturbance, poorly recognized by physicians in this setting. Shock states, sepsis, multifactorial systemic inflammatory response syndrome and ischemia-reperfusion injury are associated with important metabolic changes that contribute to this disturbance. As a result, the lipid concentration, including cholesterol, high- density lipoproteins and apo-lipoprotein A-I, diminishes. Previous reports correlate the disturbance in lipids with a higher risk of infection, systemic inflammatory response syndrome, multiple organic dysfunction syndrome and raised mortality. The use of reconstituted high-density lipoprotein may be a therapeutic alternative for the management of this entity.
Article: HDL and endothelial protection.[Show abstract] [Hide abstract]
ABSTRACT: High density lipoproteins (HDLs) represent a family of particles characterized by the presence of apolipoprotein A-I (apoA-I) and by their ability to reverse transport cholesterol from peripheral tissues back to the liver. In addition to this function, HDLs display pleiotropic effects including antioxidant, anti-apoptotic, anti-inflammatory, anti-thrombotic or anti-proteolytic properties that account for their protective action on endothelial cells (ECs). Vasodilatation via production of nitric oxide (NO) is also a hallmark of HDL action on ECs. ECs express receptors for apoA-I/HDLs that mediate intracellular signalling and potentially participate in the internalization of these particles. In this review, we will detail the different effects of HDLs on the endothelium in normal and pathological conditions with a particular focus on the potential use of HDL therapy to restore endothelial function and integrity.British Journal of Pharmacology 03/2013; DOI:10.1111/bph.12174 · 4.99 Impact Factor