Abstract
Epidemiological experimental and clinical data support a primary atherogenic role for plasma low density lipoproteins (LDL) (1). The mechanism by which LDL are mostly cleared form the blood circulation is the LDL receptor pathway which is normally regulated by a feedbak mechanism thus preventing the accumulation of cholesterol esters in the cell (2). This pathway is altered in familial hypercholesterolemia (FH). The homozygous form of FH, in which LDL receptors are severely deficient (10%), occurs in only one subject out of every milion. Heterozygotes, with a consistent reduction of receptors (50%), represent one out of every 500 persons (3). Among patients with myocardial infarction under age 60 5% have a genetic defect of the LDL specific receptors (3). It happens therefore that coronary atherosclerosis, as well the others pictures of the clinical atherosclerosis, is mostly present in people having a normal receptorial system. The accumulation of cholesteryl esters in the foam cells, the peculiar trait of the atherosclerotic plaque, has to happen therefore through other pathways. Foam cells derive from two cellular sources: the arterial smooth muscle cells (SMC) and the monocytes-derived macrophages (MM) (4).
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Kaππel WB, Castelli WP, Gordon T and McNamara PM (1971). Serum cholesterol, lipoproteins and the risk of coronary heart disease. Ann Intern Med 74, 1
Goldstein JL and Broun MG (1977). Low density lipoprotein pathway and its relation to atherosclerosis. Aππu Rev Biochem 46, 897
Goldstein JL and Brown MS (1983). Familial hypercholesterolemia. In: Stanbury JB, Wyngaarden JB, Fredrickson DS, Goldstein JL and Brown MS (eds.). “The metabolic basis of inherited disease. V”. (McGraw Hill Co) p. 672
Ross R (1981). Atherosclerosis: a problem of the biology of arterial wall cells and their interactions with blood components. Arteriosclerosis 1, 293
Goldstein JL, Ho YK, Basu SK and Brown MS (1979). Binding site on macrophages that mediates uptake and degradation of acetylated low density lipoproteins, producing massive cholesterol ester deposition. Proc Natl Acad Sci USA 76, 333
Stein O and Stein Y (1980). Bovine aortic endothelial cells display macrophage-like properties towards acetylated 125I- labelled low density lipoproteins. Biochim Biophys Acta 620, 631
Goldstein JL and Brown MS (1982). Insights into the pathogenesis of atherosclerosis derived from studies of familial hypercholesterolemia. In: Carlson LA and Pernow B (Eds.). “Metabolic risk factors in ischemic cardiovascular disease”. (Raven Press, New York) p. 17
Fogelmaπ AM, Shechter I, Seager J, Hokam M, Childs JS and Edwards PA (1980). Maloπdialdehyde alteration of low density lipoproteins leads to cholesterol ester accumulation in human moπocyte-derived macrophages. Proc Nat Acad Sci USA 7, 2214
Henriksen T, Mahoney E and Steinberg D (1981). Enhanced macrophage degradation of low density lipoprotein previously incubated with cultured endothelial cells: recognition by receptors for acetylated low density lipoprotein. Proc Nat Acad Sci USA 78, 649
Hessler JR, Morel DW, Lewis JL and Chisolm GM (1983). Lipoprotein oxidation and lipoprotein-induced cytotoxicity. Arteriosclerosis 3, 213
Henriksen T, Evenseπ SA and Carlander B (1979). Injury to human endothelial cells in culture induced by low density lipoproteins. Scand J Clin Lab Invest 39, 361
Schuh J, Novogzodisky A and Haschemeyer RH (1978). Inhibition of lymphocite mitogenesis by autoxidized low density lipoproteins. Biochem Biophys Res Comm 84, 763
Steinbrecher UP, Parthasazathy S, Leake DS, Witzum JL and Steinberg D (1984). Modification of low density lipoproteins by endothelial cells involves lipid peroxidation and degradation of low density lipoprotein phospholipids. Proc Natl Acad Sci USA 81, 3883
Nishigaki I, Hagihara H, Tusunekawa H, Maseki M and Yagi K (1981). Lipid peroxide levels of serum lipoprotein fractions of diabetic patients. Biochem Med 25, 373
Goto Y (1982). Lipid peroxides as a cause of vascular diseases. In: Yagi K (ed.) “Lipid peroxides in biology and medicine”. (Academic Press Inc., New York) p. 295
Bittolo Bon G, Cazzolato G and Avogaro P (1983). Cjaπges of apolipoprotein B molecular weight and immunoreactivity in malondialdehyde-modified low density lipoproteins. Artery 12, 74
Bittolo Bon G, Cazzolato G, Zago S and Avogaro P (1985). Effects of pantethine on in-vitro peroxidation of low density lipoproteins. Atherosclerosis 57, 99
Hoff HF (1979). LDL with altered surface charge: a new risk factor in atherogenesis? Artery 6, 178
Pryor WA, Castle L (1984). Chemical methods for detection of lipid hydroperoxides. In: Packer L (ed.) “Methods in Enzymology 105: oxigen radicals in biological systems”. (Academic Press) p. 293
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1987 MTP Press Limited
About this chapter
Cite this chapter
Avogaro, P., Bon, G.B., Cazzolato, G. (1987). Modified LDL in humans. In: Lenzi, S., Descovich, G.C. (eds) Atherosclerosis and Cardiovascular Diseases. Springer, Dordrecht. https://doi.org/10.1007/978-94-009-3205-0_11
Download citation
DOI: https://doi.org/10.1007/978-94-009-3205-0_11
Publisher Name: Springer, Dordrecht
Print ISBN: 978-94-010-7938-9
Online ISBN: 978-94-009-3205-0
eBook Packages: Springer Book Archive