Immunological evidence for the accumulation of lipoprotein(a) in the atherosclerotic lesion of the hypoascorbemic guinea pig.
Abstract
Lipoprotein(a) [Lp(a)] is an extremely atherogenic lipoprotein. Lp(a) has been found in the plasma of humans and other primates, but until now only in a few other species. The mechanism by which it exerts its atherogenicity is still poorly understood. We observed that Lp(a) has been found in the plasma of several species unable to synthesize ascorbate and not in other species. We have now detected apoprotein(a) in the plasma of the guinea pig. We induced atherosclerosis in this animal by dietary ascorbate depletion and, using SDS/PAGE and subsequent immunoblotting, we identified Lp(a) as accumulating in the atherosclerotic plaque. Most importantly, adequate amounts of ascorbate (40 mg per kg of body weight per day) prevent the development of atherosclerotic lesions in this animal model and the accumulation of Lp(a) in the arterial wall. We suggest an analogous mechanism in humans because of the similarity between guinea pigs and humans with respect to both the lack of endogenous ascorbate production and the role of Lp(a) in human atherosclerosis.
Full text
Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (982K), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.
Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- McLean JW, Tomlinson JE, Kuang WJ, Eaton DL, Chen EY, Fless GM, Scanu AM, Lawn RM. cDNA sequence of human apolipoprotein(a) is homologous to plasminogen. Nature. 1987 Nov 12;330(6144):132–137. [PubMed] [Google Scholar]
- Gonzalez-Gronow M, Edelberg JM, Pizzo SV. Further characterization of the cellular plasminogen binding site: evidence that plasminogen 2 and lipoprotein a compete for the same site. Biochemistry. 1989 Mar 21;28(6):2374–2377. [PubMed] [Google Scholar]
- Loscalzo J, Weinfeld M, Fless GM, Scanu AM. Lipoprotein(a), fibrin binding, and plasminogen activation. Arteriosclerosis. 1990 Mar-Apr;10(2):240–245. [PubMed] [Google Scholar]
- Brown MS, Goldstein JL. Plasma lipoproteins: teaching old dogmas new tricks. Nature. 1987 Nov 12;330(6144):113–114. [PubMed] [Google Scholar]
- Armstrong VW, Cremer P, Eberle E, Manke A, Schulze F, Wieland H, Kreuzer H, Seidel D. The association between serum Lp(a) concentrations and angiographically assessed coronary atherosclerosis. Dependence on serum LDL levels. Atherosclerosis. 1986 Dec;62(3):249–257. [PubMed] [Google Scholar]
- Költringer P, Jürgens G. A dominant role of lipoprotein(a) in the investigation and evaluation of parameters indicating the development of cervical atherosclerosis. Atherosclerosis. 1985 Dec;58(1-3):187–198. [PubMed] [Google Scholar]
- Rath M, Niendorf A, Reblin T, Dietel M, Krebber HJ, Beisiegel U. Detection and quantification of lipoprotein(a) in the arterial wall of 107 coronary bypass patients. Arteriosclerosis. 1989 Sep-Oct;9(5):579–592. [PubMed] [Google Scholar]
- Niendorf A, Rath M, Wolf K, Peters S, Arps H, Beisiegel U, Dietel M. Morphological detection and quantification of lipoprotein(a) deposition in atheromatous lesions of human aorta and coronary arteries. Virchows Arch A Pathol Anat Histopathol. 1990;417(2):105–111. [PubMed] [Google Scholar]
- Rath M, Pauling L. Hypothesis: lipoprotein(a) is a surrogate for ascorbate. Proc Natl Acad Sci U S A. 1990 Aug;87(16):6204–6207. [PMC free article] [PubMed] [Google Scholar]
- Ginter E, Babala J, Cerven J. The effect of chronic hypovitaminosis C on the metabolism of cholesterol and atherogenisis in guinea pigs. J Atheroscler Res. 1969 Nov-Dec;10(3):341–352. [PubMed] [Google Scholar]
- Nambisan B, Kurup PA. Ascorbic acid and glycosaminoglycan and lipid metabolism in guinea pigs fed normal and atherogenic diets. Atherosclerosis. 1975 Nov-Dec;22(3):447–461. [PubMed] [Google Scholar]
- Neville DM., Jr Molecular weight determination of protein-dodecyl sulfate complexes by gel electrophoresis in a discontinuous buffer system. J Biol Chem. 1971 Oct 25;246(20):6328–6334. [PubMed] [Google Scholar]
- Beisiegel U, Schneider WJ, Brown MS, Goldstein JL. Immunoblot analysis of low density lipoprotein receptors in fibroblasts from subjects with familial hypercholesterolemia. J Biol Chem. 1982 Nov 10;257(21):13150–13156. [PubMed] [Google Scholar]
- Constantinides P. The role of arterial wall injury in atherogenesis and arterial thrombogenesis. Zentralbl Allg Pathol. 1989;135(6):517–530. [PubMed] [Google Scholar]
- Gore I, Fujinami T, Shirahama T. Endothelial changes produced by ascorbic acid deficiency in guinea pigs. Arch Pathol. 1965 Oct;80(4):371–376. [PubMed] [Google Scholar]
- Frei B, England L, Ames BN. Ascorbate is an outstanding antioxidant in human blood plasma. Proc Natl Acad Sci U S A. 1989 Aug;86(16):6377–6381. [PMC free article] [PubMed] [Google Scholar]
- Jialal I, Vega GL, Grundy SM. Physiologic levels of ascorbate inhibit the oxidative modification of low density lipoprotein. Atherosclerosis. 1990 Jun;82(3):185–191. [PubMed] [Google Scholar]


