Ascorbic acid and glycosaminoglycan and lipid metabolism in guinea pigs fed normal and atherogenic diets

Nambisan, Bala; Kurup, Parameswara Achutha

doi:10.1016/0021-9150(75)90024-6

Cited by 54 publications

(26 citation statements)

References 21 publications

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“…The guinea pig has not been used widely as experimental model of atherosclerosis. However, it has been reported that atherosclerosic lesions could be induced in this animal fed a diet low in ascorbate (Nambisan and Kurup 1975;Bath and Pauling 1990). Very recently, Rath and Pauling (1990) pointed out the analogies between the guinea pig and the human system, and emphasized that the guinea pig should be an ideal model for future atherosclerosis research.…”

Section: Resultsmentioning

confidence: 70%

Does chylomicronemia cause atherosclerosis?

Okubo¹,

Hara

1991

Tohoku J. Exp. Med.

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105MURASE, T., OKUBO, M. and HARA, M. Does Chylomicronemia Cause Atherosclerosis. Tohoku J. Exp. Med., 1991, 163 (2), 129-134 Does chylomicronemia cause atherosclerosis ? To directly address this clinically important problem, we conducted experiments in guinea pigs which lack apolipoprotein CII and develop chylomicronemia when they are fed a high-fat diet. After 6-12 months on a high-fat diet, guinea pigs were sacrificed, and subjected to histopathological and ultrastructual examination. Both the aorta and the coronary arteries revealed no atherosclerotic changes in all 4 animals examined : the endothelium was intact, and neither lipid-laden foam cells nor migrating cells were present within the arterial wall. Our studies indicate that chylomicronemia does not predispose to atherosclerosis. chylomicronemia ; arterial wall ; high-fat diet ; guinea pigs

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Section: Resultsmentioning

confidence: 70%

Does chylomicronemia cause atherosclerosis?

Okubo¹,

Hara

1991

Tohoku J. Exp. Med.

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“…It was therefore of interest to look for Lp(a) in the plasma of the guinea pig. Earlier studies had shown that ascorbate deficiency induces atherosclerosis in the guinea pig (10,11). This is in contrast to most other species, where atherosclerosis must be induced by a high-fat diet or other atherogenic stimuli.…”

mentioning

confidence: 74%

“…It is likely that ascorbate deficiency increases the infiltration of all lipoproteins into the arterial wall due to the disintegration of the endothelial cell lining and the impairment of the extracellular matrix at low ascorbate concentrations (11,19). In accordance with our hypothesis that apo(a) is a surrogate for ascorbate, Lp(a) accumulation in the arterial wall would be a consequence of the cellular and extracellular disintegration caused by a decrease of tissue ascorbate concentrations.…”

Section: Discussionmentioning

confidence: 99%

Immunological evidence for the accumulation of lipoprotein(a) in the atherosclerotic lesion of the hypoascorbemic guinea pig.

Rath

Pauling

1990

Proc. Natl. Acad. Sci. U.S.A.

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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.Lipoprotein(a) [Lp(a)] is a low density lipoprotein particle with an additional glycoprotein named apoprotein (a) [apo(a)]. The cDNA sequence of apo(a) shows a striking homology of apo(a) and plasminogen with multiple repeats of kringle 4, one kringle 5, and a protease domain (1). Lp(a) competitively inhibits the binding of plasminogen to immobilized fibrin, fibrinogen, and the plasminogen receptor on endothelial cells (2), and it attenuates clot lysis induced by tissue-type plasminogen activator (3). Therefore Lp(a) was assumed to be the missing link between atherosclerosis and thrombosis (4). Lp(a) has been shown in various epidemiological studies to be positively associated with coronary heart disease and other forms of atherosclerosis (5, 6). Furthermore, a significant positive correlation between Lp(a) concentrations in human plasma and arterial wall has been established (7) and the development of atherosclerotic lesions correlates with the degree of Lp(a) deposition in the arterial wall (8).We observed that Lp(a) had primarily been found in the plasma of species that have lost the ability to synthesize ascorbate and we have consequently formulated the hypothesis that Lp(a) is a surrogate for ascorbate (9). According to this hypothesis ascorbate and Lp(a) share common properties, such as the promotion of cell repair, and would be able to replace one another under physiological and pathophysiological conditions. In addition to humans and other primates, the guinea pig is known to have lost the ability to synthesize ascorbate. It was therefore of interest to look for Lp(a) in the plasma of the guinea pig. Earlier studies had shown that ascorbate deficiency induces atherosclerosis in the guinea pig (10,11). This is in contrast to most other species, where atherosclerosis must be induced by a high-fat diet or other atherogenic stimuli. It was therefore of particular interest to determine whether Lp(a) would also be found in the atherosclerotic lesion of ...

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“…However, additional AA inhibited the reduction in LPL activity and the associated elevation of TG levels. In contrast, Nambisan and Kurup [16] found the LPL activity in the aorta to be independent of the AA concentration. EFFECT OF AA ON LIPID PEROXIDATION Lipid peroxidation and oxidative modification of LDL have been proposed as important steps in the atherosclerotic process.…”

Section: Effect Of Aa On Lipid Metabolismmentioning

confidence: 96%

“…In contrast, a decrease in the cholesterol level of the serum, liver and aorta was observed in weanling rats fed a large dose of AA for one month [ 15] . Similarly, in guinea pigs receiving an atherogenic diet, high doses of AA resulted in reductions in liver and aorta cholesterol levels and serum triglyceride (TG) levels [16].…”

Section: Effect Of Aa On Lipid Metabolismmentioning

confidence: 99%