Failure to produce atherosclerosis in Macaca radiata on a high-methionine, high-fat, pyridoxine-deficient diet

Krishnaswamy, Kamala; Rao, Spriha

doi:10.1016/0021-9150(77)90033-8

Cited by 20 publications

(5 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This finding has not been confirmed by Donahue et al (6) and Makheja et al (14). Similarly, high-methionine high-fat diet in pyridoxinedeficient monkeys failed to induce athero sclerosis (13) in contradiction to the results o f Rinehart et al (19). Meanwhile, it is difficult to expect atherosclerotic changes in rabbits after such short treatments (20 days, 35 days, 3 months) even in the presence o f increased permeability.…”

Section: Discussioncontrasting

confidence: 56%

Methionine, Pyridoxine and Endothelial Lesion in Rats

Hladovec¹

1980

J Vasc Res

View full text Add to dashboard Cite

Methionine administered orally to rats produced a prolonged dose-dependent increase in endothelemia. The increase was observed after doses exceeding 100 mg/kg and was inhibited by a simultaneous administration of pyridoxine. The effect of methionine was also inhibited by trihydroxyethylrutoside and acetylsalicylic acid. Endothelemia was increased furthermore by oral administration of cysteine and cystine and this increase was again inhibited by pyridoxine.

show abstract

Section: Discussioncontrasting

confidence: 56%

Methionine, Pyridoxine and Endothelial Lesion in Rats

Hladovec¹

1980

J Vasc Res

View full text Add to dashboard Cite

show abstract

“…Generally, however, hyperhomocysteinemia is not in itself atherogenic in experimental animals fed a normal low-fat diet, including nonhuman primates (20,21,62,63), rabbits (64), rats (65) (66), and mice (67). However, all of these animals have relatively low plasma cholesterol levels and none develop atherosclerosis spontaneously to any significant degree.…”

Section: Homocysteine and Atherothrombosis: Experimental Observationsmentioning

confidence: 96%

Homocysteine and atherothrombosis

Falk

Zhou

Møller

2001

Lipids

View full text Add to dashboard Cite

Atherosclerosis with or without thrombosis superimposed is the most frequent cause of ischemic heart disease (IHD), peripheral arterial disease, and a main cause of stroke. Conflicting results have been reported in genetic, observational, and experimental studies on the relationship between homocysteine and these atherothrombotic diseases. Although cardiovascular complications are common in homocystinuric patients (severe hyperhomocysteinemia), IHD, the most frequent manifestation of atherothrombosis in the general population, appears to be rare. On the basis of findings in individuals with hyperhomocysteinemia of genetic origin, there is in fact no clear evidence for a causal role of homocysteine in the pathogenesis of atherothrombotic disease, and the positive association between plasma homocysteine and IHD observed in many, but not all epidemiologic studies does not prove causality. To infer causality from observational studies, there should be a temporal, consistent, strong, independent, graded (dose-response effect), and duration-dependent relationship between exposure and outcomes, and a biologically plausible mechanism should exist. The relationship between plasma homocysteine levels and IHD does not fulfill these criteria beyond reasonable doubt. In the general population, plasma homocysteine levels are to a great extent determined by dietary habits, and plasma homocysteine could be a marker, or a consequence, of atherothrombosis and/or risk-associated behavior (e.g., a diet low in fruits and vegetables) rather than a cause of atherothrombosis. Experimentally, hyperhomocysteinemia is not in itself atherogenic in normal animals with relatively low plasma cholesterol levels. The homocysteine theory of atherosclerosis should be tested more thoroughly in hypercholesterolemic animals that develop atherosclerosis spontaneously to determine whether elevated plasma homocysteine levels are harmful under atherogenic conditions. A causal role of homocysteine in atherothrombotic disease remains to be established.

show abstract

“…Some clinical studies have also reported the involvement of mild homocysteinemia (15 to 35 mol/l) in the development of atherosclerotic lesions (14). Moreover, Hcy has been shown to induce inhibition of endothelium-dependent relaxation from rat aorta (15) as well as arteriosclerosislike alterations on baboons (16), rhesus monkeys (17), pigs (18), and rats (19). Taken together, these different observations have contributed in establishing that hyperhomocysteinemia constitutes an independent risk factor for atherosclerosis (20), but the underlying pathophysiological mechanisms leading to vascular injuries remain to be elucidated.…”

mentioning

confidence: 98%

Efficiency of homocysteine plus copper in inducing apoptosis is inversely proportional to γ‐glutamyl transpeptidase activity

et al. 2001

View full text Add to dashboard Cite

Hyperhomocysteinemia represents an independent risk factor for atherosclerosis, but the mechanisms leading to cellular dysfunctions remain unknown. Using ECV304 cells, we found that homocysteine (Hcy) plus copper (Cu2+) induced cytotoxic effects: loss of cell adhesion, increased permeability to PI, and the occurrence of morphologically apoptotic cells. This form of apoptosis, inhibited by Z-VAD-fmk, was associated with a loss of mitochondrial potential, a cytosolic release of cytochrome c, activation of caspase-3, degradation of poly(ADP-ribose)polymerase, and internucleosomal DNA fragmentation. However, the ability of Hcy plus Cu2+ to induce apoptosis decreased when the pretreatment culture time increased. As a positive correlation was found between the length of time of culture before treatment and the enhancement of gamma-glutamyl transpeptidase (gamma-GT) activity, we asked whether gamma-GT was involved in the control of Hcy plus Cu2+-induced apoptosis. Therefore, ECV304 cells were treated with either acivicin or dexamethasone, inhibiting and stimulating gamma-GT, respectively. In ECV304 cells and human umbilical venous endothelial cells, acivicin favored Hcy plus Cu2+-induced apoptosis whereas dexamethasone counteracted the apoptotic process. As acivicin and dexamethasone were also capable of modulating cell death in ECV304 cells treated with antitumoral drugs, our data emphasize that the involvement of gamma-GT in the control of apoptosis is not restricted to Hcy but also concerns other chemical compounds.

show abstract

Failure to produce atherosclerosis in Macaca radiata on a high-methionine, high-fat, pyridoxine-deficient diet

Cited by 20 publications

References 15 publications

Methionine, Pyridoxine and Endothelial Lesion in Rats

Methionine, Pyridoxine and Endothelial Lesion in Rats

Homocysteine and atherothrombosis

Efficiency of homocysteine plus copper in inducing apoptosis is inversely proportional to γ‐glutamyl transpeptidase activity

Contact Info

Product

Resources

About