Elevated circulating levels of soluble CD‐40 ligand in haemodialysis patients with symptomatic coronary heart disease

Lim, Paik‐Seong; Wu, Ming-Ying; Chien, Shiaw-Wen; Wu, Tingfeng; Liu, Chia-Shan; Hu, Chuen-Yuh; Chang, Hui‐Chen; Pai, Mei-An Tsai

doi:10.1111/j.1440-1797.2008.00999.x

Cited by 14 publications

(7 citation statements)

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“…It is mostly generated by activated platelets and elevated in stage-5 CKD patients with CVD. 40 Consistent with our findings, sCD40L levels were found to be elevated in HHcy patients and positively correlated with Hcy. 36 Our study is the first to connect CD40L elevation with MC differentiation and to validate this connection in experimental models.…”

Section: Discussionsupporting

confidence: 92%

Chronic Kidney Disease Induces Inflammatory CD40 ⁺ Monocyte Differentiation via Homocysteine Elevation and DNA Hypomethylation

Yang

et al. 2016

Circulation Research

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Rationale Chronic kidney disease (CKD) patients develop hyperhomocysteinemia (HHcy) and have a higher cardiovascular mortality than those without HHcy by 10-fold. Objective We investigated monocyte (MC) differentiation in human CKD and cardiovascular disease (CVD). Methods and Results We identified CD40 as a CKD-related MC activation gene using CKD-MC-mRNA array analysis and classified CD40 MC (CD40+CD14+) as a stronger inflammatory subset than the intermediate MC (CD14++CD16+) subset. We recruited 27 CVD/CKD patients and 14 healthy subjects and found that CD40/CD40 classical/CD40 intermediate MC (CD40+CD14+/CD40+CD14++CD16−/CD40+CD14++CD16+), plasma homocysteine (Hcy), S-adenosylhomocysteine (SAH) and S-adenosylmethionine (SAM) levels were higher in CVD and further elevated in CVD+CKD. CD40 and CD40 intermediate subsets were positively correlated with plasma/cellular Hcy levels and SAH and SAM but negatively correlated with estimated glomerular filtration rate (eGFR). HHcy was established as a likely mediator for CKD-induced CD40 intermediate MC, and reduced SAH/SAM was established for CKD-induced CD40/CD40 intermediate MC. Soluble CD40 ligand (sCD40L), TNFα/IL-6/IFNγ levels were elevated in CVD/CKD. CKD serum/Hcy/CD40L/TNFα/IL-6/IFNγ-induced CD40/CD40 intermediate MC in PBMC. Hcy and CKD serum-induced CD40 MC were prevented by neutralizing antibodies against CD40L/TNFα/IL-6. DNA hypomethylation was found on NFκB consensus element in CD40 promoter in WBC from CKD patients with lower SAM/SAH ratios. Finally, Hcy inhibited DNA methyltransferase-1 activity and promoted CD40 intermediate MC differentiation which was reversed by folic acid in PBMC. Conclusion CD40 MC is a novel inflammatory MC subset that appears to be a biomarker for CKD severity. HHcy mediates CD40 MC differentiation via sCD40L induction and CD40 DNA hypomethylation in CKD.

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Section: Discussionsupporting

confidence: 92%

Chronic Kidney Disease Induces Inflammatory CD40 ⁺ Monocyte Differentiation via Homocysteine Elevation and DNA Hypomethylation

Yang

et al. 2016

Circulation Research

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“…sCD40L ligand concentrations are associated with an increased risk of cardiovascular events in the general population 56 and are increased in patients with MHD. 57 We found that sCD40L increased during dialysis and there was no difference among the treatment arms. Koh et al also reported that 2 months of treatment with candesartan reduced the plasma levels of sCD40L in hypertensive patients.…”

Section: Discussionmentioning

confidence: 64%

Comparative Effects of Angiotensin-Converting Enzyme Inhibition and Angiotensin-Receptor Blockade on Inflammation during Hemodialysis

Gamboa¹,

Pretorius²,

Todd-Tzanetos³

et al. 2012

Journal of the American Society of Nephrology

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Biomarkers of oxidative stress and inflammation predict cardiovascular events in maintenance hemodialysis patients. Angiotensin-converting enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs) reduce cardiovascular mortality in the general population, but their benefit in maintenance hemodialysis patients is not fully explored. To test whether ACE inhibitors and ARBs differentially affect markers of oxidative stress, inflammation, and fibrinolysis during hemodialysis, we conducted a randomized, doubleblind, placebo-controlled 333 crossover study. We randomly assigned 15 participants undergoing hemodialysis to placebo, ramipril (5 mg/d), and valsartan (160 mg/d) for 7 days, with a washout period of 3 weeks in between the treatments. On the morning of the seventh day of drug treatment, participants underwent serial blood sampling during hemodialysis. Neither ramipril nor valsartan affected BP during hemodialysis. Ramipril increased IL-1b concentrations (P=0.02) and decreased IL-10 concentrations (P=0.04) compared with placebo. Valsartan and ramipril both lowered IL-6 levels during dialysis (P,0.01 for each compared with placebo). Valsartan increased F 2 -isoprostane levels, and ramipril suggested a similar trend (P=0.09). Valsartan and ramipril both lowered D-dimer levels (P,0.01 for both), whereas only ramipril seemed to prevent a rise in vWf levels (P=0.04). In summary, during hemodialysis, valsartan induces a greater anti-inflammatory effect compared with ramipril, although ramipril seems to prevent dialysis-induced endothelial dysfunction as measured by levels of vWf. A prospective clinical trial is necessary to determine whether ACE inhibitors and ARBs also differ with respect to their effects on cardiovascular mortality in this population. 23: 334-342, 201223: 334-342, . doi: 10.1681 In ESRD patients, cardiovascular death accounts for .50% of overall mortality and the risk of cardiovascular death is 30 times higher than in the general population. 1,2 Moreover, patients undergoing maintenance hemodialysis (MHD) have a 5-year survival rate of 10% after acute myocardial infarction. 3 Traditional risk factors, as used in Framingham risk scoring, only explain half of the excessive cardiovascular mortality observed in ESRD patients, 4 and it is thought that other factors contribute to the high cardiovascular mortality among ESRD patients. J Am Soc NephrolIncreased oxidative stress and inflammation may contribute to accelerated atherosclerosis and cardiovascular events in patients with MHD. 5,6 Markers of oxidative stress, such as F 2 -isoprostanes, are increased in MHD patients. 7,8 Inflammatory markers, particularly IL-1, IL 6, and TNFa, are also elevated in MHD patients and are associated with

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“…Protein carbonylation plays an important role in the etiology and/or progression of several human diseases such as cardiovascular and neurodegenerative diseases [39]. PC was significantly elevated in patients with symptomatic coronary heart disease (CHD) in end-stage renal disease on maintenance hemodialysis (HD) compared to those without [40]. In the present study, LS and HS supplementation markedly increased PC over no supplementation regardless of MeHg treatment and these increases in PC were not associated with increases in other serum markers except ICAM-1 examined.…”

Section: Discussionmentioning

confidence: 99%

Dietary Selenium (Se) and Vitamin E (VE) Supplementation Modulated Methylmercury-Mediated Changes in Markers of Cardiovascular Diseases in Rats

et al. 2011

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Epidemiological studies demonstrated that human exposure to methylmercury (MeHg) may contribute to the development and progression of metabolic and cardiovascular disorders. However, the mechanisms involved and the role of selenium (Se) and vitamin E (V(E)) supplementation in modulating MeHg cardiovascular toxicities remain unclear. This study examined the effects of Se and V(E) supplementation on MeHg-mediated systemic oxidative stress, antioxidant defense, inflammation, and endothelial dysfunction in an animal model. Male Sprague-Dawley rats were fed a starch-based casein diet or the same diet supplemented with 1 or 3 mg Se/kg diet and with or without 250 or 750 mg V(E)/kg diet. After 28 days of dietary treatment, rats were gavaged with 0 or 3 mg MeHg/kg BW for 14 consecutive days. Results suggested that exposure to MeHg may increase the risk of cardiovascular disease by decreasing circulating paraoxonase-1 activities, increasing serum oxidized low density lipoprotein levels, and associated systemic inflammation and endothelial dysfunction as reflected by increased leukocyte counts and serum levels of intercellular adhesion molecule-1 and monocyte chemotactic protein-1. Se and V(E) supplementation may either alleviate or augment the effects of MeHg, depending on their doses and combinations.

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Elevated circulating levels of soluble CD‐40 ligand in haemodialysis patients with symptomatic coronary heart disease

Abstract: Circulating concentrations of sCD40L were elevated in HD patients with symptomatic CHD. This study suggests that CD40-CD40L may play a potentially important role in the atherosclerotic complications of HD patients.

Cited by 14 publications

References 50 publications

Chronic Kidney Disease Induces Inflammatory CD40 ⁺ Monocyte Differentiation via Homocysteine Elevation and DNA Hypomethylation

Chronic Kidney Disease Induces Inflammatory CD40 ⁺ Monocyte Differentiation via Homocysteine Elevation and DNA Hypomethylation

Comparative Effects of Angiotensin-Converting Enzyme Inhibition and Angiotensin-Receptor Blockade on Inflammation during Hemodialysis

Dietary Selenium (Se) and Vitamin E (VE) Supplementation Modulated Methylmercury-Mediated Changes in Markers of Cardiovascular Diseases in Rats

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Elevated circulating levels of soluble CD‐40 ligand in haemodialysis patients with symptomatic coronary heart disease

Abstract: Circulating concentrations of sCD40L were elevated in HD patients with symptomatic CHD. This study suggests that CD40-CD40L may play a potentially important role in the atherosclerotic complications of HD patients.

Cited by 14 publications

References 50 publications

Chronic Kidney Disease Induces Inflammatory CD40 + Monocyte Differentiation via Homocysteine Elevation and DNA Hypomethylation

Chronic Kidney Disease Induces Inflammatory CD40 + Monocyte Differentiation via Homocysteine Elevation and DNA Hypomethylation

Comparative Effects of Angiotensin-Converting Enzyme Inhibition and Angiotensin-Receptor Blockade on Inflammation during Hemodialysis

Dietary Selenium (Se) and Vitamin E (VE) Supplementation Modulated Methylmercury-Mediated Changes in Markers of Cardiovascular Diseases in Rats

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Resources

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Chronic Kidney Disease Induces Inflammatory CD40 ⁺ Monocyte Differentiation via Homocysteine Elevation and DNA Hypomethylation

Chronic Kidney Disease Induces Inflammatory CD40 ⁺ Monocyte Differentiation via Homocysteine Elevation and DNA Hypomethylation