Overloading human aortic smooth muscle cells with low density lipoprotein-cholesteryl esters reproduces features of atherosclerosis in vitro.
Human aortic smooth muscle cells accumulate only small amounts of cholesteryl esters in tissue culture, even when incubated for prolonged periods with high levels of plasma low density lipoprotein (LDL). This failure to overaccumulate LDL-cholesteryl esters is due to an LDL-mediated feedback suppression of the activity of the cell surface LDL receptor, a regulatory action that limits the rate at which the cells take up LDL. This regulatory system can be bypassed by incubating smooth muscle cells with LDL that has been given a strong positive charge by covalent linkage with N,N-dimethyl-1,3-propanediamine (DMPA-LDL). The unregulated uptake of DMPA-LDL produces a massive deposition of cholesteryl esters in the form of inclusions within the cell. These inclusions take up lipid stains and exhibit positive birefringence with formée crosses that are typical of liquid crystals of cholesteryl esters. By electron microscopy, the cholesteryl ester inclusions appear as homogeneous gray cytoplasmic lipid droplets. The current studies demonstrate that the unregulated uptake of LDL-cholesteryl esters by human aortic smooth muscle cells can reproduce in vitro the major biochemical and morphological alterations that occur within smooth muscle cells in vivo during the process of atherosclerosis.
D001013:Aorta, Thoracic / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D001018:Aortic Diseases / Q000209:etiology; D001161:Arteriosclerosis / Q000209:etiology / Q000473:pathology; D002784:Cholesterol / Q000031:analogs & derivatives*; D002788:Cholesterol Esters / Q000378:metabolism*; D003959:Diamines; D006801:Humans; D007223:Infant; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008854:Microscopy, Electron; D008859:Microscopy, Polarization; D008954:Models, Biological; D009130:Muscle, Smooth / Q000166:cytology / Q000378:metabolism; D011955:Receptors, Drug / Q000502:physiology; D013329:Structure-Activity Relationship
D002788:Cholesterol Esters; D003959:Diamines; D008077:Lipoproteins, LDL; D011955:Receptors, Drug; D002784:Cholesterol; C012928:3-dimethylaminopropylamine