Circulating P-, L- and E-selectins in pseudoxanthoma elasticum patients

Götting, Christian; Adam, Alexandra; Szliska, Christiane; Kleesiek, Knut

doi:10.1016/j.clinbiochem.2007.12.009

Cited by 8 publications

(3 citation statements)

References 45 publications

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“…A primary role for smooth muscle cells and fibroblasts in PXE is suspected as they are a source of many regulatory proteins involved in the calcification process such as alkaline phosphatase and MGP (Shanahan et al, 1999; Simionescu et al, 2005). Finally, an abnormal balance between elevated proteolysis activity with increased P-selectin (Gotting et al, 2008), matrix metallo-proteinase (MMP) 2 and 9 (Diekmann et al, 2009), suggests an abnormal remodeling of the extra cellular matrix (ECM) in PXE. Despite unknown mechanism sequence for elastosis and calcification, the nature and affected sites of calcification lead to different functional expression.…”

Section: The Vascular Lesions and Histological Findings In Pxementioning

confidence: 99%

The vascular phenotype in Pseudoxanthoma elasticum and related disorders: contribution of a genetic disease to the understanding of vascular calcification

Lefthériotis¹,

Omarjee²,

Saux³

et al. 2013

Front. Gene.

100

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Vascular calcification is a complex and dynamic process occurring in various physiological conditions such as aging and exercise or in acquired metabolic disorders like diabetes or chronic renal insufficiency. Arterial calcifications are also observed in several genetic diseases revealing the important role of unbalanced or defective anti- or pro-calcifying factors. Pseudoxanthoma elasticum (PXE) is an inherited disease (OMIM 264800) characterized by elastic fiber fragmentation and calcification in various soft conjunctive tissues including the skin, eyes, and arterial media. The PXE disease results from mutations in the ABCC6 gene, encoding an ATP-binding cassette transporter primarily expressed in the liver, kidneys suggesting that it is a prototypic metabolic soft-tissue calcifying disease of genetic origin. The clinical expression of the PXE arterial disease is characterized by an increased risk for coronary (myocardial infarction), cerebral (aneurysm and stroke), and lower limb peripheral artery disease. However, the structural and functional changes in the arterial wall induced by PXE are still unexplained. The use of a recombinant mouse model inactivated for the Abcc6 gene is an important tool for the understanding of the PXE pathophysiology although the vascular impact in this model remains limited to date. Overlapping of the PXE phenotype with other inherited calcifying diseases could bring important informations to our comprehension of the PXE disease.

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Section: The Vascular Lesions and Histological Findings In Pxementioning

confidence: 99%

The vascular phenotype in Pseudoxanthoma elasticum and related disorders: contribution of a genetic disease to the understanding of vascular calcification

Lefthériotis¹,

Omarjee²,

Saux³

et al. 2013

Front. Gene.

100

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“…Furthermore, C13 was associated with the integrin-mediated signalling pathway ( P = 5.15e−07) and polyarthritis ( P = 1.74e−03); a significant contribution of integrin to inflammatory cartilage destruction has previously been reported ( Peters et al , 2012 ). Finally, C18 was associated with cell adhesion ( P = 4.98e−05) and Pseudoxanthoma elasticum infection ( P = 6.63e−09); elevated levels of the cell adhesion molecule P-selectin have been observed in patients infected with P. elasticum ( Gotting et al , 2008 ). These results demonstrate the usefulness of domain-based functional networks for studying the underlying molecular mechanisms of diseases.…”

Section: Resultsmentioning

confidence: 99%

Weighted mutual information analysis substantially improves domain-based functional network models

Shim

Lee

2016

Bioinformatics

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Motivation: Functional protein–protein interaction (PPI) networks elucidate molecular pathways underlying complex phenotypes, including those of human diseases. Extrapolation of domain–domain interactions (DDIs) from known PPIs is a major domain-based method for inferring functional PPI networks. However, the protein domain is a functional unit of the protein. Therefore, we should be able to effectively infer functional interactions between proteins based on the co-occurrence of domains.Results: Here, we present a method for inferring accurate functional PPIs based on the similarity of domain composition between proteins by weighted mutual information (MI) that assigned different weights to the domains based on their genome-wide frequencies. Weighted MI outperforms other domain-based network inference methods and is highly predictive for pathways as well as phenotypes. A genome-scale human functional network determined by our method reveals numerous communities that are significantly associated with known pathways and diseases. Domain-based functional networks may, therefore, have potential applications in mapping domain-to-pathway or domain-to-phenotype associations.Availability and Implementation: Source code for calculating weighted mutual information based on the domain profile matrix is available from www.netbiolab.org/w/WMI.Contact: Insuklee@yonsei.ac.krSupplementary information: Supplementary data are available at Bioinformatics online.

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“…There is also an ‘elastosis hypothesis' in PXE that implicates abnormal elastin turnover as the primary defect, and calcification of the medial wall smooth muscle cells as a secondary consequence [29,30,31]. Of note, breakage of elastic fibers is present in the aortic wall of CKD mice [32,33], and fragmentation of medial elastic fibers has been described in CKD patients [34,35].…”

Section: Discussionmentioning

confidence: 99%

Chronic Kidney Disease Results in Deficiency of ABCC6, the Novel Inhibitor of Vascular Calcification

Lau

Liu²,

Vaziri³

2014

Am J Nephrol

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Background: Chronic kidney disease (CKD) is associated with arterial medial calcification which plays a major role in the pathogenesis of cardiovascular disease in this population. Several factors are known to promote soft tissue and accelerated arterial calcification in CKD including systemic inflammation, altered calcium and phosphate homeostasis, hypertension, and deficiency of endogenous calcification inhibitors. The ABCC6 transporter (ATP-binding cassette subfamily C number 6), also known as multidrug resistance-associated protein 6 (MRP6), is highly expressed in the liver and kidney. Mutation of ABCC6 results in pseudoxanthoma elasticum, an inherited disorder characterized by arterial and soft tissue calcification. Given the prevalence of arterial medial calcification in CKD, the present study was undertaken to test the hypothesis that CKD may lead to acquired ABCC6 deficiency. Methods: CKD was induced via 5/6 nephrectomy in male Sprague-Dawley rats and by adenine-containing diet to cause chronic interstitial nephropathy in female DBA/2J mice. Sham-operated rats and mice fed regular diet served as controls. Liver and kidney tissues were harvested and processed for ABCC6 protein and mRNA analysis. Results: ABCC6 protein levels were significantly reduced in the liver and kidney tissues from CKD rats and mice. However, ABCC6 mRNA levels were unchanged, pointing to post-transcriptional or post-translational mechanisms for the observed ABCC6 deficiency. Additionally, plasma levels of the calcification inhibitor fetuin-A were significantly decreased in CKD animals compared to controls. Conclusions: CKD results in acquired ABCC6 transporter deficiency. To our knowledge this abnormality has not been previously reported and may contribute to CKD-associated vascular and soft tissue calcification.

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Circulating P-, L- and E-selectins in pseudoxanthoma elasticum patients

Cited by 8 publications

References 45 publications

The vascular phenotype in Pseudoxanthoma elasticum and related disorders: contribution of a genetic disease to the understanding of vascular calcification

The vascular phenotype in Pseudoxanthoma elasticum and related disorders: contribution of a genetic disease to the understanding of vascular calcification

Weighted mutual information analysis substantially improves domain-based functional network models

Chronic Kidney Disease Results in Deficiency of ABCC6, the Novel Inhibitor of Vascular Calcification

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