Lipolysis Produces Changes in the Immunoreactivity and Cell Reactivity of Very Low Density Lipoproteins

Abstract

A B S T R A C T Smaller very low density lipoprotein (VLDL) remnants interact more readily with tissues than do larger "intact" VLDL. This may be related to changes in the availability of VLDL apoproteins on the surface of the lipoproteins. To test this hypothesis VLDL were incubated at 37°C with bovine milk lipase (LPL), and the abilities of LPL-treated VLDL preparations to compete with 1251-low density lipoproteins (LDL) for interaction with cultured normal human fibroblasts were measured. At the same time, the immunologic activities of these preparations were also tested by double antibody radioimmunoassay. Triglyceride (TG) contents of VLDL fell by 30-90% during incubation with LPL and, on zonal ultracentrifugation, VLDL of faster Svedberg unit of flotation (Sfl.063) rates (>150) were gradually converted to smaller VLDL with lower Sf rates (21-60).LPL-treated VLDL competed two to five times more effectively with 1251-LDL for binding to cellular receptors than did control VLDL. Control VLDL incubated with heat-inactivated LPL at 37°C, or with active LPL at 4°C had unaltered cell reactivities and TG contents compared with VLDL incubated without any enzyme. The direct uptake and degradation of LPLtreated VLDL was also assessed by using VLDL 125I1 labeled in apoprotein (Apo)B. LPL-treated VLDL-1251-ApoB were taken up and degraded by fibroblast at greater rates than were control VLDL-'25I-ApoB. Thus, hydrolysis of VLDL lipids was accompanied by an increased ability of VLDL to interact with fibroblasts. The immunoreactivity of ApoB in the same VLDL preparations, expressed as the "apparent ApoB contents" of LPL-treated VLDL, increased by 10-50% (P <0.02) in those assays that contained anti-LDL antisera, but the ApoB of control VLDL remained constant. However, assays that contained antisera directed against ApoB isolated from VLDL did not distinguish Received for publication 7 August 1978 and in revised form 9 July 1979. 1288 between LPL-treated and control VLDL. Thus, VLDL lipid hydrolysis was accompanied by changes in the immunoreactivity of VLDL-ApoB, which probably reflect changes in the disposition of ApoB on the surface of VLDL. The altered disposition of ApoB on VLDL "remnants" may be related to their enhanced interaction with cells.

Plasma lipoproteins in familial hepatic lipase deficiency.

“…Schonfeld et al 31 have shown that treatment of subclasses of VLDL with lipoprotein lipase increased the expression of apo B-dependent binding to fibroblast apo B,E receptors. Recently, Aviram et al 3 2 3 3 have shown that modification of triglyceride-enriched LDL by HL enhances degradation of LDL by fibroblast apo B,E receptors.…”

Very low density lipoproteins promote triglyceride accumulation in macrophages.

“…Such products of VLDL catabolism have manifested enhanced interactions with fibroblasts and smooth muscle cells in culture when compared to the original triglyceride-rich lipoprotein particle. 50 " 53 Although atherosclerotic plaques contain predominantly cholesterol rather than triglyceride, triglyceride accumulation may be a transient phenomenon in the evolution of the atherosclerotic lesion. The remnants remaining after the hydrolysis of triglycerides within the triglyceride-rich chylomicron and VLDL particles may contribute to the cholesterol of the lesion cells.…”

Lipoprotein Lipase Binds to Low Density Lipoprotein Receptors and Induces Receptor-mediated Catabolism of Very Low Density Lipoproteins

“…Lipolysis may expose or activate the receptor-recognition domains of apoE or apoB100 and contribute to LPL's effect (53)(54)(55)(56)(57). This is consistent with the finding that the lipid component of lipoprotein particles may modulate the reactivity of the apoprotein component (58).…”