Platelet proinflammatory activity in clinically stable patients with CF starts in early childhood

Sturm, A.; Hebestreit, Helge; Koenig, Corinne; Walter, Ulrich; Grossmann, Ralf

doi:10.1016/j.jcf.2009.12.004

Cited by 10 publications

(10 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Sturm et al found a higher sP-selectin concentration in 54 CF patients—including children—compared with 55 age- and sex-matched healthy subjects [21]. In the subgroup of subjects aged 15–41 years the values compared as follows ( n CF = 28; n HS = 29): 41 ng/mL [25–56] versus 29 ng/mL [17–60].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Increased Soluble VCAM-1 and Normal P-Selectin in Cystic Fibrosis: a Cross-Sectional Study

Nowak

Wojsyk‐Banaszak

Mądry

et al. 2017

Lung

View full text Add to dashboard Cite

PurposeAs life expectancy in cystic fibrosis (CF) increases, questions regarding its potential impact on cardiovascular health arise. Soluble vascular cell adhesion molecule 1 (sVCAM-1), P-selectin (sP-selectin) are proposed as biomarkers of cardiovascular disease. We aimed to: compare their concentrations in clinically stable CF patients and healthy subjects (HS) and verify whether they independently correlate with CF characteristics.MethodsSerum sVCAM-1 and sP-selectin levels were measured using ELISA. CF was characterized using: forced expiratory volume in 1 s, exocrine pancreatic and CF-related liver disease status, Pseudomonas aeruginosa colonization, serum high-sensitivity C-reactive protein, and body mass index (BMI). CFTR genotypes were classified as severe (classes I and II) or other.Results108 CF patients and 51 healthy subjects volunteered for the study. In the CF group BMI was lower (median [IQR]: 20.5 kg/m2 [18.4–22.2] vs. 21.6 kg/m2 [19.9–23.4], p = 0.02) and hsCRP levels were higher (3.6 mg/L [1.1–7.1] vs. 0.5 mg/dL [0.3–1.0], p < 10−10). While sVCAM-1 concentrations were greater in CF patients (1018 ng/mL [851–1279] vs. 861 ng/mL [806–979], p < 10−4), sP-selectin levels did not differ (155 ng/mL [129–188] vs. 156 ng/mL [144–177], p = 0.48). None of the multivariable regression models was valid for the prediction of sVCAM-1 and sP-selectin in CF.ConclusionsWe found higher sVCAM-1 concentrations in CF patients than in healthy subjects, which were not explained by CF characteristics. Further research is required to check whether sVCAM-1 is a marker of microangiopathy in CF.

show abstract

Section: Discussionmentioning

confidence: 99%

“…However, in the same subjects, they found normal levels of sVCAM-1. An inverse correlation between forced expiratory volume in 1 s (FEV1) and sP-selectin was also described [20] as well as higher sP-selectin levels in CF compared with healthy controls [21]. The above findings come from few studies with moderate sample sizes.…”

Section: Introductionmentioning

confidence: 99%

Increased Soluble VCAM-1 and Normal P-Selectin in Cystic Fibrosis: a Cross-Sectional Study

Nowak

Wojsyk‐Banaszak

Mądry

et al. 2017

Lung

View full text Add to dashboard Cite

show abstract

“…The early onset of chronic inflammation in the CF patients is mainly mediated by neutrophils and even platelets have been suggested [42]. Proinflammatory molecules of the innate immune system such as IL-1, IL-6 and IL-8 are elevated in CF, all of which could be regulated by serine peptidases.…”

Section: Discussionmentioning

confidence: 99%

Reduced levels of active GLP-1 in patients with cystic fibrosis with and without diabetes mellitus

Hillman

Eriksson

Mared

et al. 2012

Journal of Cystic Fibrosis

View full text Add to dashboard Cite

Glucagon like peptide 1 (GLP-1) is an incretin hormone released as a bioactive peptide from intestinal L-cells in response to eating. It acts on target cells and exerts several functions as stimulating insulin and inhibiting glucagon. It is quickly deactivated by the serine protease dipeptidyl peptidase IV (DPP-IV) as an important regulatory mechanism. GLP-1 analogues are used as antidiabetic drugs in patients with type 2 diabetes. We served patients with cystic fibrosis (CF, n=29), cystic fibrosis related diabetes (CFRD, n=19) and healthy controls (n=18) a standardized breakfast (23 g protein, 25 g fat and 76 g carbohydrates) after an overnight fasting. Blood samples were collected before meal as well as 15, 30, 45 and 60 min after the meal in tubes prefilled with a DPP-IV inhibitor. The aim of the study was to compare levels of GLP-1 in patients with CF, CFRD and in healthy controls. We found that active GLP-1 was significantly decreased in patients with CF and CFRD compared to in healthy controls (p<0.01). However, levels in patients with CFRD tended to be lower but were not significantly lower than in patients with CF without diabetes (p=0.06). Total GLP-1 did not differ between the groups, which points to that the inactive form of GLP-1 is more pronounced in CF patients. The endogenous insulin production (measured by C-peptide) was significantly lower in patients with CFRD as expected. However, levels in non-diabetic CF patients did not differ from the controls. We suggest that the decreased levels of GLP-1 could affect the progression toward CFRD and that more studies need to be performed in order to evaluate a possible treatment with GLP-1 analogues in CF-patients.

show abstract

“…These data provide further evidence for platelet defects in CF which to date CF have included increased aggregability, alterations in cell lipids, decreased exocytosis, and decreased integrin binding. [4, 5] Our techniques appear sound as blood cytokine levels, VEGF and TGF-β 1 release measured during platelet aggregation, and correlation coefficients of serum VEGF and TGF-β 1 with platelet number in healthy controls are typical of those reported in other investigations. [22, 24, 32–35]…”

Section: Discussionmentioning

confidence: 60%

“…As others have reported, we found platelet counts, maximal platelet aggregation, plasma TGF-β 1 and VEGF, and unadjusted serum levels of TGF-β 1 and VEGF to be higher in CF patients. [5, 24] However, when we adjusted serum levels for platelet counts we found no differences between CF and healthy subjects. [21] This differs from the situation seen in cancer patients, where the platelet content of VEGF has also been shown to be increased in subjects with high serum VEGF levels even after adjustment for platelet counts.…”

Section: Discussionmentioning

confidence: 92%

Decreased TGF-β1 and VEGF Release in Cystic Fibrosis Platelets: Further Evidence for Platelet Defects in Cystic Fibrosis

Maloney

Narasimhan²,

Biller

2016

Lung

View full text Add to dashboard Cite

Purpose Cystic fibrosis (CF) patients suffer from chronic lung inflammation. This inflammation may activate platelets. There are limited data on the role of platelet-secreted cytokines in CF. Platelet cytokines with inflammatory effects include vascular endothelial growth factor (VEGF) and transforming growth factor-β1 (TGF-β1). As levels of these cytokines are tenfold greater in serum than plasma due to platelet release, serum levels may be one index of platelet content; but a more specific index is release during the aggregation of isolated platelets. We postulated that altered release of these platelet cytokines occurs in CF. Methods We obtained sera and plasma from CF outpatients (n=21) and from healthy controls (n=20), measured VEGF and TGF-β1, assessed for correlations with platelet number, analyzed cytokine release during platelet aggregation to collagen, and analyzed differences in maximal platelet aggregation. Results Platelet number and maximal aggregation levels were higher in CF. Plasma and serum levels of TGF-β1 and VEGF were higher in CF, but these levels were similar after adjusting for platelet number (serum cytokines correlated with platelet count). The release of VEGF and TGF-β1 during aggregation was decreased in CF platelets (by 52% and 29%, respectively). Conclusion Platelet release is not a source of the elevated blood proinflammatory cytokines TGF-β1 and VEGF in CF, as platelets from CF patients actually release less of these cytokines. These data provide further evidence for platelet defects in CF.

show abstract

Platelet proinflammatory activity in clinically stable patients with CF starts in early childhood

Abstract: In CF, platelet proinflammatory activity is increased at very young age already and might promote inflammation and tissue damage. On the other hand, platelets seem to downregulate the activation of their most important integrin (alpha(IIb)beta(3)) for clot formation.

Cited by 10 publications

References 30 publications

Increased Soluble VCAM-1 and Normal P-Selectin in Cystic Fibrosis: a Cross-Sectional Study

Increased Soluble VCAM-1 and Normal P-Selectin in Cystic Fibrosis: a Cross-Sectional Study

Reduced levels of active GLP-1 in patients with cystic fibrosis with and without diabetes mellitus

Decreased TGF-β1 and VEGF Release in Cystic Fibrosis Platelets: Further Evidence for Platelet Defects in Cystic Fibrosis

Contact Info

Product

Resources

About