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Verfasst von:Bartosova, Maria [VerfasserIn]   i
 Schäfer, Betti [VerfasserIn]   i
 Lorenzo Bermejo, Justo [VerfasserIn]   i
 Lasitschka, Felix [VerfasserIn]   i
 Sinn, Peter [VerfasserIn]   i
 Schaefer, Franz [VerfasserIn]   i
 Schmitt, Claus P. [VerfasserIn]   i
Titel:Complement activation in peritoneal dialysis-induced arteriolopathy
Verf.angabe:Maria Bartosova, Betti Schaefer, Justo Lorenzo Bermejo, Silvia Tarantino, Felix Lasitschka, Stephan Macher-Goeppinger, Peter Sinn, Bradley A. Warady, Ariane Zaloszyc, Katja Parapatics, Peter Májek, Keiryn L. Bennett, Jun Oh, Christoph Aufricht, Franz Schaefer, Klaus Kratochwill and Claus Peter Schmitt
Jahr:2018
Umfang:15 S.
Fussnoten:Published online December 29, 2017 ; Gesehen am 02.10.2018
Titel Quelle:Enthalten in: American Society of NephrologyJournal of the American Society of Nephrology
Ort Quelle:Washington, DC : American Society of Nephrology, 1990
Jahr Quelle:2018
Band/Heft Quelle:29(2018), 1, Seite 268-282
ISSN Quelle:1533-3450
Abstract:Visual Overview <img class="highwire-fragment fragment-image" alt="Figure1" src="https://jasn.asnjournals.org/content/jnephrol/29/1/268/F1.medium.gif" width="440" height="330"/>Download figureOpen in new tabDownload powerpoint Cardiovascular disease (CVD) is the leading cause of increased mortality in patients with CKD and is further aggravated by peritoneal dialysis (PD). Children are devoid of preexisting CVD and provide unique insight into specific uremia- and PD-induced pathomechanisms of CVD. We obtained peritoneal specimens from children with stage 5 CKD at time of PD catheter insertion (CKD5 group), children with established PD (PD group), and age-matched nonuremic controls (n=6/group). We microdissected omental arterioles from tissue layers not directly exposed to PD fluid and used adjacent sections of four arterioles per patient for transcriptomic and proteomic analyses. Findings were validated in omental and parietal arterioles from independent pediatric control (n=5), CKD5 (n=15), and PD (n=15) cohorts. Transcriptomic analysis revealed differential gene expression in control versus CKD5 arterioles and in CKD5 versus PD arterioles. Gene ontology analyses revealed activation of metabolic processes in CKD5 arterioles and of inflammatory, immunologic, and stress-response cascades in PD arterioles. PD arterioles exhibited particular upregulation of the complement system and respective regulatory pathways, with concordant findings at the proteomic level. In the validation cohorts, PD specimens had the highest abundance of omental and parietal arteriolar C1q, C3d, terminal complement complex, and phosphorylated SMAD2/3, a downstream effector of TGF-β. Furthermore, in the PD parietal arterioles, C1q and terminal complement complex abundance correlated with the level of dialytic glucose exposure, abundance of phosphorylated SMAD2/3, and degree of vasculopathy. We conclude that PD fluids activate arteriolar complement and TGF-β signaling, which quantitatively correlate with the severity of arteriolar vasculopathy.
DOI:doi:10.1681/ASN.2017040436
URL:Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.

Volltext: http://dx.doi.org/10.1681/ASN.2017040436
 Volltext: https://jasn.asnjournals.org/content/29/1/268
 DOI: https://doi.org/10.1681/ASN.2017040436
Datenträger:Online-Ressource
Sprache:eng
Sach-SW:arteriosclerosis
 children
 complement
 peritoneal dialysis
 TGF-beta
 vascular disease
K10plus-PPN:1581507313
Verknüpfungen:→ Zeitschrift

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