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Increased plasma chymase concentration and mast cell chymase expression in venous neointimal lesions of patients with

Haimanot Wasse1, Angel A Rivera, Rong Huang

  • 1Division of Nephrology, Emory University, Atlanta, Georgia 30322, USA. hwasse@emory.edu

Seminars in Dialysis
|July 26, 2011
PubMed

Insights

Mast cell chymase contributes to intimal hyperplasia (IH), a key factor in dialysis access failure. Targeting chymase may offer a novel therapeutic strategy for chronic kidney disease patients.

Area of Science:

  • Vascular Biology
  • Nephrology
  • Inflammation

Background:

  • Chronic kidney disease (CKD) involves inflammation that may promote intimal hyperplasia (IH), leading to dialysis access failure.
  • Intimal hyperplasia (IH) is a significant cause of arteriovenous (AV) fistula dysfunction in patients requiring dialysis.

Purpose of the Study:

  • To investigate the role of mast cell chymase in the development of vascular pathology and IH in patients with CKD and end-stage renal disease (ESRD).
  • To determine if markers of IH formation, specifically chymase, are present before AV fistula creation.

Main Methods:

  • Vessel segments from CKD and ESRD patients were analyzed using immunohistochemistry for mast cell chymase, TGF-β, and IL-6.
  • Plasma chymase levels were quantified using ELISA in CKD patients and controls.
  • Presence and localization of chymase within vascular tissue were correlated with IH and plasma concentrations.

Main Results:

  • Intimal hyperplasia (IH) was prevalent in 91% of CKD and 75% of ESRD patient vein segments.
  • Mast cell chymase was highly expressed in vessels with IH, particularly in the intima and medial layers, and colocalized with TGF-β1 and IL-6.
  • Plasma chymase concentrations were significantly elevated (up to 33-fold) in CKD patients compared to controls and correlated with vascular chymase expression.

Conclusions:

  • Mast cell chymase is significantly expressed in the vascular lesions of CKD and ESRD patients, suggesting its involvement in intimal hyperplasia (IH).
  • Elevated plasma chymase levels in CKD patients correspond to increased chymase within IH lesions.
  • Chymase inhibition presents a potential therapeutic avenue for preventing or treating intimal hyperplasia (IH) and improving dialysis access outcomes in patients with kidney disease.

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