Elevated circulating levels and tissue expression of pentraxin 3 in uremia: a reflection of endothelial dysfunction

PLoS One. 2013 May 3;8(5):e63493. doi: 10.1371/journal.pone.0063493. Print 2013.

Abstract

Elevated systemic pentraxin 3 (PTX3) levels appear to be a powerful marker of inflammatory status and a superior outcome predictor in patients with chronic kidney disease (CKD). As previous data imply that PTX3 is involved in vascular pathology and that adipose tissue mass may influence circulating PTX3 levels, we aimed to study the importance of adipose tissue expression of PTX3 in the uremic milieu and its relation to endothelial dysfunction parameters. Plasma PTX3 and abdominal subcutaneous adipose tissue (SAT) PTX3 mRNA levels were quantified in 56 stage 5 CKD patients (median age 57 [range 25-75] years, 30 males) and 40 age and gender matched controls (median age 58 [range 20-79] years, 27 males). Associations between PTX3 measures and an extensive panel of clinical parameters, including surrogate markers of endothelial function, were assessed. Functional ex vivo studies on endothelial status and immunohistochemical staining for PTX3 were conducted in resistance subcutaneous arteries isolated from SAT. SAT PTX3 mRNA expression correlated with plasma PTX3 concentrations (rho = 0.54, p = 0.0001) and was increased (3.7 [0.4-70.3] vs. 1.2 [0.2-49.3] RQ, p = 0.02) in CKD patients with cardiovascular disease (CVD), but was not significantly different between patients and controls. The association to CVD was lost after adjustments. SAT PTX3 mRNA levels were independently correlated to asymmetric dimethylarginine and basal resistance artery tone developed after inhibition with nitric oxide synthase and cyclooxygenase (rho = -0.58, p = 0.002). Apparent positive PTX3 immunoreactivity was observed in both patient and control arteries. In conclusion, fat PTX3 mRNA levels are associated with measures of endothelial cell function in patients with CKD. PTX3 may be involved in adipose tissue-orchestrated mechanisms that are restricted to the uremic milieu and modify inflammation and vascular complications in CKD patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Arginine / analogs & derivatives
  • Arginine / metabolism
  • Biomarkers / metabolism
  • C-Reactive Protein / genetics
  • C-Reactive Protein / metabolism*
  • Cardiovascular Diseases / complications
  • Cardiovascular Diseases / metabolism*
  • Cardiovascular Diseases / physiopathology
  • Case-Control Studies
  • Endothelium / metabolism*
  • Endothelium / physiopathology
  • Female
  • Gene Expression
  • Humans
  • Kidney / metabolism*
  • Kidney / physiopathology
  • Male
  • Middle Aged
  • Prognosis
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism*
  • Renal Insufficiency, Chronic / complications
  • Renal Insufficiency, Chronic / metabolism*
  • Renal Insufficiency, Chronic / physiopathology
  • Serum Amyloid P-Component / genetics
  • Serum Amyloid P-Component / metabolism*
  • Subcutaneous Fat, Abdominal / metabolism
  • Subcutaneous Fat, Abdominal / pathology
  • Uremia / etiology
  • Uremia / metabolism*
  • Uremia / physiopathology
  • Vascular Resistance

Substances

  • Biomarkers
  • RNA, Messenger
  • Serum Amyloid P-Component
  • PTX3 protein
  • N,N-dimethylarginine
  • C-Reactive Protein
  • Arginine

Grant support

This study is supported by The Strategic Research Programme in Diabetes at Karolinska Institutet (Swedish Research Council 2009-1068) and grants from Swedish Research Council (15320-07-6; 2011-2349) (PS, JJS), Centre for Gender Medicine at Karolinska Institutet (PS, JJS, KK) as well as from Stiftelsen Olle Engkvist Byggare (FH). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.