2-Chlorodeoxyadenosine in combination with cyclosporine inhibits the development of transplant arteriosclerosis in rat cardiac allografts

Cramer, Donald V.; Wu, GS; Chapman, Frances A.; Marboe, C.; Salomon, Daniel R.

doi:10.1016/s0041-1345(97)82533-x

Cited by 4 publications

(4 citation statements)

References 2 publications

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“…Indeed, it was demonstrated that decreased adenosine levels are associated with enhanced proliferation or growth of vascular smooth muscle cells and sclerotic changes in arteries or glomeruli. 26 Limitations of our study include singlecenter, homogenous population and small sample size. In conclusion Hcys metabolism is altered in children with FENS.…”

Section: Discussionmentioning

confidence: 93%

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Homocysteine Metabolism in Children with Idiopathic Nephrotic Syndrome

Kundal

Saha

Dubey

et al. 2014

Clinical Translational Sci

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Background: Homocysteine metabolism is altered in children with idiopathic nephrotic syndrome. Hyperhomocysteinemia is a risk factor of early atherosclerosis and glomerulosclerosis and may occur at time of first occurrence of idiopathic nephrotic syndrome. Methods: Thirty children with first episode of idiopathic nephrotic syndrome (FENS) aged 1-16 years along with 30 age-and sexmatched healthy controls were enrolled in this study. Homocysteine and cysteine were measured with HPLC; vitamin B 12 and folic acid were measured with electro-chemilumiscence immunoassay. Primary outcome measure was plasma homocysteine level in children with FENS and in controls. Secondary outcome measures were (1) plasma and urine homocysteine and cysteine levels in children with FENS at 12 weeks and 1 year (remission) and (2) plasma and urine levels of vitamin B 12 and folic acid in children with FENS, at 12 weeks and 1 year (remission). Results: Plasma homocysteine and cysteine levels were comparable to controls in children with FENS, at 12 weeks and 1-year remission. Plasma levels of vitamin B12 and folic acid were significantly decreased compared to controls in FENS due to increased urinary excretion, which normalize during remission at 12 weeks and 1 year. Urinary homocysteine and cysteine levels were significantly raised in FENS compared to controls and continued to be raised even at 12-week and 1-year remission. Conclusion: Homocysteine metabolism is deranged in children with FENS. Renal effects of long-term raised urinary homocysteine levels need to be studied. Clin Trans Sci 2014; Volume 7: 132-136

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Section: Discussionmentioning

confidence: 93%

“…It is possible that the sclerotic effect of hHcys is associated with decreased adenosine. Indeed, it was demonstrated that decreased adenosine levels are associated with enhanced proliferation or growth of vascular smooth muscle cells and sclerotic changes in arteries or glomeruli …”

Section: Discussionmentioning

confidence: 99%

Homocysteine Metabolism in Children with Idiopathic Nephrotic Syndrome

Kundal

Saha

Dubey

et al. 2014

Clinical Translational Sci

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“…Indeed, recent studies in our laboratory and by others have demonstrated that decreased adenosine levels are associated with enhanced proliferation or growth of vascular smooth muscle cells and sclerotic changes in arteries or glomeruli. 19,33,34 More recently, it has been reported that hHcys is one of the most important mechanisms resulting in cardiovascular complications in chronic renal diseases. 35 In this regard, Hcys-induced renal dysfunction or glomerular injury observed in the present study may represent an early pathological abnormality resulting in arteriosclerosis and cardiovascular diseases.…”

Section: Discussionmentioning

confidence: 99%

Effect of Hyperhomocysteinemia on Plasma or Tissue Adenosine Levels and Renal Function

Chen

Zou

2002

Circulation

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Background-Hyperhomocysteinemia (hHcys) is considered an independent risk factor of cardiovascular diseases. Recent studies in our laboratory have shown that hHcys produced glomerular dysfunction and sclerosis independently of hypertension. However, the mechanism mediating these pathogenic effects of homocysteine (Hcys) is poorly understood. Because Hcys and adenosine (Ado) are simultaneously produced via hydrolysis of S-adenosylhomocysteine (SAH), we hypothesized that hHcys may produce its pathogenic effects by decrease in plasma or tissue Ado concentrations. Methods and Results-L-Hcys (1.5 mol/min per kilogram) was infused intravenously for 60 minutes to produce acute hHcys in Sprague-Dawley rats. Plasma Hcys levels increased from 6.7Ϯ0.4 to 14.7Ϯ0.5 mol/L, but Ado decreased from 141.7Ϯ15.1 to 52.4Ϯ6.8 nmol/L in these rats with acute hHcys. This hHcys-induced reduction of Ado was also observed in the kidney dialysate. In rats with chronic hHcys, plasma Ado levels were also significantly decreased. By kinetic analysis of the enzyme activities, decrease in renal Ado levels in hHcys was shown to be associated with inhibition of SAH hydrolase but not 5Ј-nucleotidase. Functionally, intravenous infusion of Hcys was found to decrease renal blood flow, glomerular filtration rate, and sodium and water excretion, which could be blocked by the Ado receptor antagonist 8-SPT. Conclusions-These results strongly suggest that hHcys decreases plasma and tissue Ado concentrations associated with inhibition of SAH hydrolase. Decrease in plasma and tissue Ado may be an important mechanism mediating the pathogenic effects of Hcys.

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“…It is possible that the sclerotic effect of hHcys is associated with decreased adenosine. Indeed, it was demonstrated [47] that decreased adenosine levels are associated with enhanced proliferation or growth of vascular smooth muscle cells and sclerotic changes in arteries or glomeruli. Decreased adenosine concentrations during hHcys may be due to an enhanced activity of a bidirectonal enzyme, SAH hydrolase.…”

Section: Potential Mechanisms Of Hcys-induced Toxicity In Glomerulimentioning

confidence: 99%

Mechanisms of Homocysteine-Induced Glomerular Injury and Sclerosis

Li²

2007

Am J Nephrol

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Hyperhomocysteinemia (hHcys) has been recognized as a critical risk or pathogenic factor in the progression of end-stage renal disease (ESRD) and in the development of cardiovascular complications related to ESRD. Recently, evidence is accumulating that hHcys may directly act on glomerular cells to induce glomerular dysfunction and consequent glomerular sclerosis, leading to ESRD. In this review, we summarize recent findings that reveal the contribution of homocysteine as a pathogenic factor to the development of glomerular sclerosis or ESRD. In addition, we discuss several important mechanisms mediating the pathogenic action of homocysteine in the glomeruli or in the kidney, such as lo- cal oxidative stress, endoplasmic reticulum stress, homocysteinylation, and hypomethylation. Understanding these mechanisms may help design new approaches to develop therapeutic strategies for treatment of hHcys-associated end-organ damage and for prevention of deterioration of kidney function and ultimate ESRD in patients with hypertension and diabetes mellitus or even in aged people with hHcys.

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2-Chlorodeoxyadenosine in combination with cyclosporine inhibits the development of transplant arteriosclerosis in rat cardiac allografts

Cited by 4 publications

References 2 publications

Homocysteine Metabolism in Children with Idiopathic Nephrotic Syndrome

Homocysteine Metabolism in Children with Idiopathic Nephrotic Syndrome

Effect of Hyperhomocysteinemia on Plasma or Tissue Adenosine Levels and Renal Function

Mechanisms of Homocysteine-Induced Glomerular Injury and Sclerosis

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