Atherogenic lipoproteins, oxidative stress, and cell death

Abstract

Atherogenic lipoproteins, oxidative stress, and cell death. bits produce relatively high amounts of O 2 Ϫ [10], and Background. Glomerulosclerosis and atherosclerosis are oxygen radicals are also involved in the pathogenesis of chronic inflammatory processes that may be influenced by oxiglomerular diseases [11]. We therefore hypothesize that dized lipoproteins, oxidized low-density lipoproteins (oxLDL), a major contribution of oxidized lipoproteins to the deand oxidized lipoprotein(a) [oxLp(a)]. We hypothesize that velopment of glomerulosclerosis and atherosclerosis these lipoproteins contribute to the development of glomerulosclerosis and atherosclerosis through the induction of oxidative consists of the induction of oxidative stress. Oxidative stress, which influences cell viability. We therefore determined stress attenuates cell viability (apoptotic and necrotic the impact of oxLDL and oxLp(a) on O 2 Ϫ formation and on cell death) [12] and, in turn, may influence the developnecrotic and apoptotic cell death in vascular and glomerular ment of glomerulosclerosis [13] and atherosclerosis. Incells. deed, vascular regions that are prone to the development Methods. The impact of human LDL and Lp(a) (oxidized with CuSO 4 ) on O 2 Ϫ formation (detected with a chemiluminesof atherosclerotic lesions are characterized by increased cence method), apoptosis, and necrosis (determined with the cell turnover during the early phase of the disease [14]. annexin assay) was studied in cultured human umbilical vein Apoptosis has also been found in human and animal endothelial cells (ECs) and in cultured human mesangial cells atherosclerotic lesions [15, 16]. It was therefore the aim (MCs). of this study to determine the impact of oxidized low-Results. O 2 Ϫ formation was increased by 10 g/ml oxLDL (by factor 2.5 in ECs) and by 5 g/ml oxLp(a) (by factor 3.5 density lipoproteins (oxLDL), and oxidized lipoproin ECs). OxLDL and oxLp(a) both significantly and dosetein(a) [oxLp(a)] on O 2 Ϫ formation and on necrotic and dependently increased the rate of apoptotic cell death in ECs apoptotic cell death in vascular and glomerular cells. and in MCs, with oxLp(a) being the more potent stimulus that also caused necrosis. The induction of apoptosis by oxLDL and oxLp(a) in ECs and MCs was enhanced by inhibition METHODS of the endogenous superoxide dismutase (SOD) with diethyldithio-carbamate and was blunted by the antioxidants N-acetyl-Human LDL and Lp(a) were isolated by density gradicysteine, vitamin C ϩ E, SOD, and catalase, suggesting that ent ultracentrifugation from fresh human plasma and, in oxidative stress was the stimulus for apoptosis.case of Lp(a), by additional lysine-sepharose 4B chroma-Conclusions. These data suggest that oxLDL and oxLp(a)

Hyperglycemia Induces Apoptosis of Human Pancreatic Islet Endothelial Cells

“…Apoptosis of islet MECs and reduced Akt phosphorylation were induced also by treatment with oxLDL, known to affect the behavior of other endothelial cells 40 and to play a major role in the pathogenesis of atherosclerosis. 41 Concomitantly, in our study, hyperglycemia down-regulated the tyrosine phosphorylated form of the transmembrane protein nephrin without affecting its cellular expression or distribution. It is known that nephrin, once phosphorylated, associates with PI3K and activates the multifunctional Akt-dependent pathways.…”

Lipid Changes and Statins in Chronic Renal Insufficiency

“…Oxidized lipids are particularly injurious in this context (29,30). Although various parameters of dyslipidemia predict accelerated progression in humans (31), a beneficial effect of statins on progression has not been documented beyond doubt.…”

Levels of Cholesteryl Esters and Other Lipids in the Plasma of Patients with End-Stage Renal Failure

“…[6][7][8][9][10][11] Second, it has long been thought that abnormalities in lipid and lipoprotein metabolism may be involved not just in the initial injury to the kidney, but also in ongoing processes that eventually lead to end-stage renal failure. [12][13][14][15] Finally, there is growing evidence that dyslipoproteinemia in the pre-transplant patient may be a contributing factor in allograft failure. [16][17][18] Most studies in renal disease have measured the main plasma lipids such as total cholesterol and triacylglycerols, together with high-density lipoprotein (HDL) cholesterol or other measures of lipoproteins.…”