Low density lipoprotein (LDL) incubated with cultured endothelial cells from rabbit aorta or human umbilical vein is altered in several ways (EC-modified): (i) It degraded by macrophages much faster than LDL similarly the absence of fibroblasts. (ii) Its electrophoretic mobility increased. (iii) We report here that antioxidants completely prevent these changes. also changes do not take place if transition metals medium are chelated EDTA. During EC-modification as 40% phosphatidylcholine to...

Previous studies in this laboratory established that low density lipoprotein (LDL) incubated with cultured endothelial cells, smooth muscle or macrophages undergoes free radical-catalyzed oxidative modification generates lipid peroxides and extensive structural changes the LDL molecule. The oxidatively modified strongly inhibited chemotactic responses of mouse resident peritoneal macrophage. present show oxidized does not inhibit motility monocytes actually exhibits a activity for human...

TODAY there is no longer any doubt about the causative relationship between hypercholesterolemia and premature atherosclerosis. The National Institutes of Health Consensus Conference on Lowering Blood Cholesterol Levels¹and Education Program that grew out it²were culmination many years experimental clinical research, including, importantly, a number positive intervention trials brought to close so-called Controversy,³ie, controversy as importance...

Oxidatively modified low density lipoprotein (LDL) exhibits several potentially atherogenic properties, and inhibition of LDL oxidation in rabbits decreases the rate development atherosclerotic lesions. In vitro studies have suggested that cellular lipoxygenases may be involved oxidation, we shown previously 15-lipoxygenase oxidized are present rabbit We now report epitopes also found macrophage-rich areas human fatty streaks as well more advanced Using situ hybridization immunostaining...

We recently reported that oxidized low density lipoprotein (OxLDL), but not acetyl LDL (AcLDL), inhibited the binding and phagocytosis of nonopsonized, oxidatively damaged red blood cells (OxRBCs) by mouse peritoneal macrophages, implying involvement a "scavenger receptor" other than AcLDL receptor. Numerous studies establish loss plasma membrane phospholipid asymmetry, which increases phosphatidylserine expression on outer leaflet membrane, can play key role in macrophage recognition...

Lipoprotein oxidation is believed to play an important role in atherogenesis. To investigate whether inhibition of low density lipoprotein (LDL) would alter atherogenesis the nonhuman primate, we administered probucol, a potent antioxidant, Macaca nemestrina fed high-fat, high-cholesterol diet. Probucol was half 16 monkeys 14 wk after starting hypercholesterolemic diet, and given daily until they were sacrificed 11 mos. evaluate antioxidant effect resistance isolated plasma LDL vitro...

The events accompanying oxidative modification of low density lipoprotein (LDL) are multiple and complex, the precise mechanisms remain to be determined. In present studies, we examined a simple system in which first prepared large amounts lipid hydroperoxides (from linoleic acid or from phospholipids containing acid) by using soybean lipoxygenase (linoleate:oxygen oxidoreductase, EC 1.13.11.12). Linoleoyl hydroperoxide was then incubated with polypeptides absence metal ions. We observed...

Oxidative modification of low density lipoprotein is believed to be an important pathway by which the becomes atherogenic. The in vitro systems for oxidative thus far described all appear depend upon presence medium free transition metal ions (copper or iron). In vivo, on other hand, these metals are present almost exclusively tightly complexed forms that do not catalyze modification. studies describe oxidation a simple system does added ions. It requires horseradish peroxidase and either...

A new kindred with asymptomatic hypobetalipoproteinemia is reported. The proband, age 67, differs from previously described cases in several respects: (a) unusually low levels of density lipoprotein (LDL) cholesterol (4-8 mg/dl); (b) normal triglyceride levels; (c) high lipoprotein; (d) mild fat malabsorption; and (e) a defect chylomicron clearance. On high-carbohydrate diet his plasma levels, instead rising, actually fell. Turnover triglycerides very lipoproteins (VLDL) was (2.8 mg/kg per...

SummaryMyocardial necrosis in humans was accompanied over 90% of the cases studied by elevation serum glutamic-oxaloacetic transaminase. Serum adenosine triphosphatase and lipoprotein lipase were not elevated. Within 36 hours after myocardial infarction transaminase levels rose to 2-10 times normal usually returned within 5 days. The ischemia angina pectoris any levels.

Swine plasma low density lipoprotein (LDL) isolated ultracentrifugally (d 1.019-1.063)was labeled with 1251, dialyzed, and reisolated by centrifugation at d 1.063.Over 96% of the radioactivity was shown to be associated apoprotein.After reinjection into donor animal, disappearance lZ5I followed for up 122 hr.At all time intervals examined, over 95% total 1251 recovered in LDL 1.006-1.063),i.e., there apparently no transfer high or very lipoproteins.The curve biexponential, half-lives 0.83 f...

Turnover of '251-low density lipoprotein (LDL) and l3II-high (HDL) was determined before after end-to-side portacaval shunt in eight swine.LDL (d 1.019-1.063)and HDL 1.09-1.21)were isolated by ultracentrifugation iodinated the iodine monochloride technique.Immediately postoperatively there no consistent change fractional catabolic rate (FCR) LDL compared to preoperative control values, while all animals FCR significantly increased (by as much 300%).After recovery from surgery, neither nor...

Macrophages contain a neutral cholesteryl ester hydrolase that can be activated by cAMP-dependent protein kinase. Immunological studies strongly suggest hormone-sensitive lipase (HSL) is probably responsible for the activity in macrophages; however, due to very low level of expression macrophages, it has been difficult determine whether macrophage and adipose HSL are, fact, products same gene. We have used sensitive polymerase chain reaction (PCR) technique demonstrate mRNA resident...

The effects of inorganic lead (PbCl2) and cadmium (DdCl2) on the pressor response rabbit saphenous arteries produced by sympathetic nerve stimulation were examined. A 1- to 3-cm length artery was removed, placed in a bath containing mammalian Ringer solution, perfused with same solution at constant rate sufficient maintain 40-60 mmHg perfusion pressure. Increases pressure resulting from electrical -f periarterial endings reduced or completely blocked addition 5-20 muM bathing for period...