Coronary Artery Disease in End-Stage Renal Disease

Stenvinkel, Peter; Pecoits‐Filho, Roberto; Lindholm, Bengt

doi:10.1097/01.asn.0000069165.79509.42

Cited by 214 publications

(183 citation statements)

References 126 publications

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“…We suspect that NF-B activation is involved in mediating the increase of ICAM-1 expression in the nonlesioned intima because the above-mentioned stimuli are all characteristically in excess in uremia. Uremic patients often have elevated plasma or tissue concentrations of proinflammatory cytokines (IL-6, TNF␣, and IL-1) (35,36), advanced glycation end products (37), and of angiotensin II (38), and they frequently display evidence of increased oxidative stress (39,40). NF-B also controls VCAM-1 expression (41).…”

Section: Discussionmentioning

confidence: 99%

Increased Expression of Adhesion Molecules in Uremic Atherosclerosis in Apolipoprotein-E–Deficient Mice

Bro¹,

Moeller²,

Andersen

et al. 2004

Journal of the American Society of Nephrology

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Abstract. Chronic renal failure markedly accelerates atherosclerosis in apolipoprotein-E-deficient mice, but the mechanism is unknown. The recruitment of inflammatory cells in the arterial wall by vascular adhesion molecules plays a key role in the formation of classical atherosclerosis. This study examines whether the expression of vascular adhesion molecules is increased in uremic atherosclerosis. Uremia was induced by 5/6 nephrectomy; control mice were sham-operated. After 2 wk of uremia, no lesion formation could be demonstrated in uremic or control mice. After 12 wk, aortas from uremic mice had a 9.8-fold increase of the aortic plaque area fraction compared with control mice (P Ͻ 0.0001). The aortic expression of intercellular adhesion molecule-1 (ICAM-1) mRNA in uremic mice was 215 Ϯ 31% (P Ͻ 0.05) and 243 Ϯ 55% (P Ͻ 0.05) of that in controls after 2 and 12 wk, respectively (n ϭ 9 ϫ 4). In contrast, aortic expression of vascular cell adhesion molecule-1 (VCAM-1) mRNA in uremic mice was unchanged after 2 wk but increased to 237 Ϯ 40% (P Ͻ 0.01) of that in control mice after 12 wk. On immunohistochemistry of aortas from uremic mice, ICAM-1 was predominantly present in endothelial cells both in nonlesioned and lesioned aortas, whereas VCAM-1 was predominantly present in the medial smooth muscle cell layer in lesioned aortas. The plasma concentration of soluble ICAM-1 (sICAM-1) (but not of sVCAM-1) was slightly elevated after 2 wk of uremia. In contrast, both sICAM-1 and sVCAM-1 plasma concentrations were markedly higher in uremic than control mice after 12 wk. These results suggest that uremic atherosclerosis is preceded by an upregulation of ICAM-1 expression in arterial endothelium and that formation of early uremic lesions is accompanied by upregulation of VCAM-1 expression in the medial smooth muscle cell layer.

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Section: Discussionmentioning

confidence: 99%

Increased Expression of Adhesion Molecules in Uremic Atherosclerosis in Apolipoprotein-E–Deficient Mice

Bro¹,

Moeller²,

Andersen

et al. 2004

Journal of the American Society of Nephrology

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“…Much interest therefore has focused on the role of nontraditional risk factors for atherosclerosis, such as inflammation and increased oxidative stress (2). The inflammatory burden is high in ESRD patients, and a wide array of inflammatory biomarkers, such as C-reactive protein (CRP), IL-6, and leukocytes, have been proved to be robust predictors of poor outcome in this patient group (2). It is known that macrophages and neutrophils may vary considerably in their level of activation, ranging from a resting to a fully activated state.…”

mentioning

confidence: 99%

Statin Treatment and Diabetes Affect Myeloperoxidase Activity in Maintenance Hemodialysis Patients

Stenvinkel

Rodríguez-Ayala

Massy

et al. 2006

Clinical Journal of the American Society of Nephrology

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Myeloperoxidase (MPO), which is secreted during activation of neutrophils, may serve as one mechanistic link among persistent inflammation, oxidative stress, and cardiovascular disease. This study related MPO activity to inflammatory and oxidative stress biomarkers, comorbidity, and ongoing medication in prevalent hemodialysis (HD) patients. In a crosssectional evaluation of 115 prevalent (vintage 25 mo) HD patients (62 men; 63 ؎ 1 yr), data on comorbidity (Davies score), diabetes, medication (statins and antihypertensive drugs), nutritional status (subjective global assessment), blood lipids (cholesterol, HDL cholesterol, and triglycerides), inflammatory biomarkers (serum albumin, C-reactive protein, TNF-␣, and IL-6), oxidative stress biomarkers (pentosidine, 8-hydroxydeoxyguanosine, and MPO activity) were recorded. Patients with MPO activity greater than the median had significantly (P < 0.05) lower serum albumin levels (33.2 ؎ 0.7 versus 35.0 ؎ 0.5 g/L), higher 8-hydroxydeoxyguanosine levels (1.26 ؎ 0.08 versus 1.05 ؎ 0.06 ng/ml), and a lower prevalence of statin treatment (18 versus 36%). Therefore, the median MPO activity was significantly (P < 0.05) lower (17.7 versus 26.6 ⌬OD630/min per mg protein) in the subgroup of 31 HD patients with ongoing statin treatment. In a multiple regression model, correction for the impact of age, gender, vintage, serum cholesterol, serum albumin, comorbidity, diabetes, and statin use, only diabetes (P < 0.01) and statin use (P < 0.01) were significantly associated to MPO activity. Fourteen patients who had diabetes and were receiving statin treatment had markedly (P ‫؍‬ 0.001) lower median (19.9 versus 41.2 ⌬OD630/min per mg protein) MPO activity compared with 18 who had diabetes and were not taking statins. This cross-sectional study suggests that both diabetes and statin treatment affect MPO activity in prevalent HD patients.

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“…Reactive oxygen species generated in oxidative stress have been found to signal the activation of TGFB1, the main inflammatory transcription factor that triggers transcription of several inflammatory mediators (Kunsch & Medford 1999). These inflammatory mediators can act in concert promoting tissue damage, particularly through leukocyte recruitment and cell proliferation (Stenvinkel et al 2003). The present study demonstrated, in vivo, that administration of EPS significantly attenuated oxidative stress in the diabetic kidney, as evidenced by a reduction in superoxide production and decrease in TBARS and AOPP in renal tissue.…”

Section: Discussionmentioning

confidence: 99%

Ethanol extraction of Picrorhiza scrophulariiflora prevents renal injury in experimental diabetes via anti-inflammation action

He¹,

Liang²,

Hou³

et al. 2008

Journal of Endocrinology

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There is evidence that inflammatory processes are involved in the development and/or progression of diabetic nephropathy. However, effective treatment for inflammation in the kidneys of diabetic is practically unknown. The rhizomes of Picrorhiza scrophulariiflora (PS) are a traditional medication long used to treat inflammatory diseases. The aim of the present study was to test the hypothesis that the ethanol extract of PS (EPS) may reduce inflammation in patients with diabetic kidneys. Streptozotocin-induced diabetic rats were randomly assigned to two groups treated with a gavage of either EPS or vehicle. A group of non-diabetic control rats was treated concurrently. Compared with vehicle-treated diabetic rats, EPS-treated animals displayed a significant decrease in renal macrophage infiltration and overexpression of chemokine (C-C motif) ligand 2 (CCL2) and TGFB1. This was associated with attenuation of the structural and functional abnormalities of early diabetic nephropathy, such as glomerular hypertrophy, mesangial expansion, and albuminuria. Administration of EPS significantly reduced NADPH oxidase-dependent superoxide generation and decreased expression of malondialdehyde and advanced oxidation protein products in diabetic kidney. These data suggest that EPS might improve diabetic nephropathy, probably through inhibition of redox-sensitive inflammation.

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Coronary Artery Disease in End-Stage Renal Disease

Cited by 214 publications

References 126 publications

Increased Expression of Adhesion Molecules in Uremic Atherosclerosis in Apolipoprotein-E–Deficient Mice

Increased Expression of Adhesion Molecules in Uremic Atherosclerosis in Apolipoprotein-E–Deficient Mice

Statin Treatment and Diabetes Affect Myeloperoxidase Activity in Maintenance Hemodialysis Patients

Ethanol extraction of Picrorhiza scrophulariiflora prevents renal injury in experimental diabetes via anti-inflammation action

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