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J Regnström

Publications and source records attributed to J Regnström.

26 records · Page 2Linked to original sources
PubMed1993

Analysis of lipoprotein diene formation in human serum exposed to copper.

The susceptibility of low density lipoprotein (LDL) to oxidative modification can be determined by analyzing the lag phase for initiation of diene formation in isolated LDL exposed to Cu2+. However, the applicability of this assay for clinical studies is limited by the requirement of a preparative ultracentrifugation of LDL and that the influence of water soluble antioxidants and other lipoproteins is not accounted for. The present paper describes a modification of this assay allowing determination of lag phase for lipoprotein diene formation in serum. The formation of dienes in serum exposed to Cu2+ begins following the consumption of serum alpha-tocopherol, correlates to the formation of thiobarbituric acid reactive substances (r = 0.987, n = 8), is inhibited by the addition of ascorbic acid and is absent in lipoprotein-deficient serum. It is also accompanied by an increased mobility of serum lipoproteins on agarose gel electrophoresis and with an ability of serum to displace isolated copper-oxidized LDL from binding sites mediating degradation in mouse peritoneal macrophages. The coefficient of variance of the analysis is below 3%. It is concluded that this technique allows analysis of lipoprotein oxidation susceptibility in serum samples and may prove to be useful in clinical analysis of the lipoprotein oxidation susceptibility.

Animals↗
PubMed1992

Susceptibility to low-density lipoprotein oxidation and coronary atherosclerosis in man.

Animal studies indicate a possible role for lipid oxidation in the development of atherosclerosis. We set out to investigate whether there was a relation between the ability of low-density lipoprotein (LDL) to resist oxidation in vitro and the severity of coronary atherosclerosis in man. 35 unselected young (mean [SD] age 39.9 [4.2] years) male survivors of myocardial infarction underwent angiography, and LDL was isolated from their plasma by density gradient ultracentrifugation. In-vitro LDL susceptibility to oxidation was assessed by determination of the lag phase for the formation of conjugated dienes in the presence of copper ions. An inverse relation was found between lag phase and quantitative estimates of global coronary atherosclerosis (r = -0.45; p less than 0.02). Multivariate analysis indicated that the lag phase for oxidative modification of LDL and LDL cholesterol concentration correlated independently with severity of coronary atherosclerosis. The lag phase for oxidation of LDL was also related to the triglyceride content of the LDL fraction (r = -0.55; p less than 0.002). The finding that susceptibility to LDL oxidation is associated with severity of coronary atherosclerosis may indicate that lipid oxidation promotes premature coronary atherosclerosis and that individuals with an LDL enriched in triglycerides are at particular risk.

Adult↗
PubMed1992

Native and oxidized LDL enhances production of PDGF AA and the surface expression of PDGF receptors in cultured human smooth muscle cells.

Animal studies have demonstrated that hypercholesterolemia leads to the development of fibromuscular atherosclerotic lesions that are characterized by the intimal accumulation of cholesterol esters in macrophage foam cells and focal proliferation of smooth muscle cells (SMCs). There is now convincing evidence that formation of foam cells occurs as a result of macrophage uptake of oxidized low density lipoprotein (LDL), but the processes linking hypercholesterolemia to activation of SMC growth are less clear. In the present study, we demonstrated that native as well as oxidized LDL stimulates DNA synthesis in cultured human SMCs. Both native and oxidized LDL enhances the expression of platelet-derived growth factor (PDGF) A-chain transcripts in the cells, suggesting that the mitogenic effect of the lipoprotein preparations may be due to activation of autocrine or paracrine PDGF loops. Preincubation of SMCs with native and oxidized LDL also increased the expression of PDGF alpha- and beta-receptors on SMCs and enhanced the responsiveness of the cells to exogenous PDGF. The maximal stimulatory effect of oxidized LDL occurred at a concentration of 3 micrograms/ml, whereas that of native LDL occurred at 10 micrograms/ml, but otherwise no difference was observed between the native and oxidized LDL preparations. The mitogenic effects of LDL disappeared if the cells were exposed to the lipoprotein preparations for more than 4 hours and was also effectively inhibited by superoxide dismutase. The present results suggest that LDL may influence the growth of SMCs by modulating the expression of growth-regulatory genes in the cells.

Cells, Cultured↗
PubMed1992

Lipid oxidation and atherosclerosis.

Hypercholesterolemia, and in particular high levels of low density lipoprotein (LDL), is a well established risk factor for development of coronary heart disease (CHD), but the biological mechanisms by which LDL promote formation of atherosclerotic plaques are still poorly understood. During the last decade several lines of evidence have suggested that oxidative modification of LDL is a key process in this respect. Oxidation of LDL has been found to increase its uptake in macrophages and lead to formation of macrophage foam cells. Other studies have indicated that oxidized LDL may induce vascular inflammation and even give rise to autoimmune reactions in the vascular wall. These findings have it made important to investigate the possible role of LDL oxidation in CHD also in clinical studies and the initial results of such studies support the notion that oxidation of LDL also may be of clinical relevance. In a group of young post-myocardial infarction patients the in vitro susceptibility of LDL to oxidative modification was found to be significantly related to the severity of coronary atherosclerosis as assessed by angiography. In another study presence of antibodies against oxidized LDL was found to be associated with increased progression of carotid disease. Should these findings be confirmed in larger patient groups and LDL oxidation established as a key factor in the development of atherosclerosis this would have a considerable impact on future strategies for prevention and treatment of coronary heart disease.

Animals↗
PubMed1990

Effect of probucol treatment on the susceptibility of low density lipoprotein isolated from hypercholesterolemic patients to become oxidatively modified in vitro.

Lipid accumulation in monocyte-originated macrophages in the subendothelial space is an important characteristic of atherosclerotic lesions. Several lines of evidence have indicated that this accumulation occurs as a result of lipid peroxidation. In the present study the ability of probucol to prevent oxidation of low density lipoprotein (LDL) was investigated in 20 hypercholesterolemic individuals taking part in the Probucol Quantitative Regression Swedish Trial (PQRST). The effect of Cu2(+)-induced oxidation of LDL on degradation by macrophages, binding to LDL receptors on fibroblasts and LDL TBARS content was analysed. With LDL isolated from patients on diet alone oxidation led to a 44.3% decreased binding to fibroblasts (P less than 0.001), a ninefold increased uptake in macrophages (P less than 0.001) and a twentyfold increase in TBARS content (P less than 0.001) as compared to native LDL. These values were essentially the same during treatment with cholestyramine alone. However, during treatment with probucol plus cholestyramine exposure of LDL to Cu2+ resulted in an increase in TBARS which was less than 50% (P less than 0.02) of that observed during the other two treatment periods. Furthermore, probucol treatment abolished more than 70% of the decrease in B,E receptor binding to fibroblasts (P less than 0.05) and more than 90% of the increased degradation by macrophages (P less than 0.001) of Cu2+ oxidatively modified LDL.

Aged↗
PubMed1984

Increase of electrophoretic mobility and of content of soluble proteins of human plasma beta-lipoproteins by incubation of plasma in vitro.

Incubation of human plasma at 37 degrees C was shown to induce an increase in the electrophoretic mobility of beta-lipoproteins. beta-Lipoproteins were isolated by density gradient ultracentrifugation after such incubation and their composition was analysed. Incubation decreased the content of free cholesterol and increased that of soluble apolipoproteins. The soluble peptides appearing in LDL upon incubation showed 3 major and 2 minor bands upon polyacrylamide disc gel electrophoresis. Two of the major bands corresponded to apolipoprotein C-III-1 and C-III-2 and one of the minor to apolipoprotein C-II. The addition of an inhibitor to lecithin:cholesterol acyltransferase (LCAT) abolished the increase in electrophoretic mobility and to a large extent diminished the other reported effects of incubation. The hypothesis is put forward that during incubation of plasma at 37 degrees C the free cholesterol in the surface of LDL is removed through the action of LCAT, lipid transferases and exchange processes and is replaced in the surface shell by peptides which cause the change in electrophoretic mobility.

Apolipoprotein C-III↗