Why Does Elevated Plasma Homocysteine Result in Severe Microvascular Injury, but Not Glomerular Damage?

Rensma, Pieter L.; Apperloo, Alfred J.; Jong, Paul E. de

doi:10.1161/01.cir.0000060817.55259.1e

Cited by 2 publications

(3 citation statements)

References 4 publications

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“…too short to produce morphological alterations in kidney. Nevertheless, these results correlate with those of Rensma et al (2003) who found no evidence of significant renal damage in patients displaying both homocystinuria and strongly elevated plasma Hcy levels (. 100 mmol/l).…”

Section: Discussionsupporting

confidence: 82%

Hyperhomocysteinaemia induced by dietary folate restriction causes kidney oxidative stress in rats

et al. 2005

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Diet is the most common cause of mild hyperhomocysteinaemia (HHcy), which occurs in approximately 5-7 % of the general population. Since HHcy causes endothelial damage by oxidative stress in different organs, the present study was designed to examine whether HHcy might be involved in renal oxidative stress. Twenty-five male Wistar rats were randomly divided into two groups: one (n 13) was fed ad libitum a folate-free diet (FF) and the other (n 12) was fed the same diet supplemented with folic acid (control, CO). After 8 weeks the animals were killed and kidneys removed. Malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities were measured in plasma and kidney homogenates. Renal tissue sections were analysed by indirect immunostaining with the primary antibody against oxidatively modified LDL receptor (LOX-1). A marked HHcy was confirmed in the FF group. As compared with CO animals, MDA levels in plasma and kidney homogenate were significantly higher in FF rats (P,0·05). Similarly, renal GPx and SOD activities were significantly higher in the FF group (P,0·001). No differences were found in LOX-1 immunohistochemical expression, which in the two groups was displayed in tubular cells. The present study provides evidence that HHcy does produce renal oxidative stress mediated by lipid peroxidation, and that the increased kidney MDA displayed by FF animals may enhance kidney antioxidant activity and thereby attenuate both kidney damage and expression of LOX-1.

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Section: Discussionsupporting

confidence: 82%

Hyperhomocysteinaemia induced by dietary folate restriction causes kidney oxidative stress in rats

et al. 2005

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“…It should be noted that results from clinical observation on the correlation of plasma Hcys concentration and kidney disease progression are controversial (13,(15)(16)(17)(18). In this regard, we had an interesting discussion with Rensma et al (17) in Circulation.…”

Section: Hyperhomocysteinemia and Glomerular Sclerosis In Rat Kidneysmentioning

confidence: 92%

“…In this regard, we had an interesting discussion with Rensma et al (17) in Circulation. Rensma et al argued that Hcys is noxious to the human vascular endothelium and that the renal microvasculature appears to be protected from this effect.…”

Section: Hyperhomocysteinemia and Glomerular Sclerosis In Rat Kidneysmentioning

confidence: 93%

Hyperhomocysteinemia – association with renal transsulfuration and redox signaling in rats

Li²

2007

Clinical Chemical Laboratory Medicine

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Despite substantial evidence indicating the association of hyperhomocysteinemia (hHcys) and end-stage renal disease (ESRD), the pathogenic role of increased plasma homocysteine (Hcys) levels in the progression of ESRD remains unclear. This review will briefly summarize recent findings regarding the role of hHcys in the development of glomerulosclerosis, the association of hHcys with reduced renal transsulfuration and Hcys-induced changes of redox signaling in the development of glomerulosclerosis in rat kidneys. Based on these results, it is concluded that hHcys is implicated in glomerular sclerosis in hypertension, elevated plasma Hcys in Dahl salt-sensitive (SS) hypertensive rats is due to downregulation of cystathionine beta-synthase (CBS) expression and consequent abnormality of transsulfuration in the kidney compared with normotensive rats. Hcys-induced superoxide (O(2)(*-)) production by activation of NADPH oxidase as a triggering mechanism contributes to the effects of Hcys on the homeostasis of extracellular matrix and consequent sclerosis in the glomeruli, and NADPH oxidase activation by Hcys is associated with enhanced Rac GTPase activity.

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Why Does Elevated Plasma Homocysteine Result in Severe Microvascular Injury, but Not Glomerular Damage?

Cited by 2 publications

References 4 publications

Hyperhomocysteinaemia induced by dietary folate restriction causes kidney oxidative stress in rats

Hyperhomocysteinaemia induced by dietary folate restriction causes kidney oxidative stress in rats

Hyperhomocysteinemia – association with renal transsulfuration and redox signaling in rats

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