Lipoprotein-heparin-fibronectin-denatured collagen complexes enhance cholesteryl ester accumulation in macrophages.

Abstract

The sequestration of low-density lipoprotein (LDL) by components of the vascular extracellular matrix was long recognized as a contributing factor to lipid accumulation during atherogenesis. The effects that components of the extracellular matrix might have on LDL catabolism by scavenger cells were little investigated. For these purposes insoluble complexes of LDL, heparin, fibronectin and denatured collagen (gelatin) were prepared and their effects examined on lipid accumulation, LDL uptake and degradation and cholesteryl ester synthesis in mouse peritoneal macrophages. These experiments demonstrated that the cholesteryl ester content of macrophages incubated with a particular suspension of LDL, heparin, fibronectin and collagen complexes is 4-5-fold that of cells incubated with LDL alone. The uptake of complexes containing 125I-LDL is rapid; however, in contrast to either endocytosed 125I-LDL or 125I-acetyl LDL, the degradation of complex-derived LDL is impaired. The uptake of complex-derived LDL stimulates the incorporation of [14C]oleic acid into cholesteryl oleate; the stimulation was a small fraction of that observed in cells incubated with acetyl LDL. Ultrastructurally, macrophages incubated with LDL, heparin, fibronectin and collagen complexes did not contain many lipid droplets, but rather their cytoplasm is filled with phagosomes containing material simmilar in appearance to LDL-matrix complexes. Components of the extracellular matrix can alter the catabolism of LDL by scavenger cells, suggesting that they may play a role in cellular lipid accumulation in the atherosclerotic lesion.