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The homeostatic chemokine CCL21 predicts mortality in aortic stenosis patients and modulates left ventricular

Alexandra Vanessa Finsen1, Thor Ueland2, Ivar Sjaastad3

  • 1Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway; Department of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, Norway; Center for Heart Failure Research, University of Oslo, Oslo, Norway.

Plos One
|November 15, 2014
PubMed

Insights

Chemokine CCL21, acting via CCR7, is elevated in aortic stenosis patients and linked to mortality. This pathway may contribute to heart remodeling during left ventricular pressure overload.

Area of Science:

  • Cardiovascular Research
  • Immunology
  • Molecular Biology

Background:

  • CCL21, a chemokine that signals through CCR7, is known for its role in immune responses and tissue remodeling.
  • Its potential involvement in myocardial remodeling under left ventricular (LV) pressure overload was investigated.

Purpose of the Study:

  • To investigate the role of the CCL21/CCR7 axis in myocardial remodeling associated with left ventricular pressure overload, particularly in the context of aortic stenosis (AS).

Main Methods:

  • Serum CCL21 levels were measured in patients with symptomatic AS and healthy controls.
  • Immunostaining was performed on human aortic valves.
  • Mice underwent experimental left ventricular pressure overload, with gene and protein expression analysis of CCL21 and CCR7.
  • CCR7 knockout mice were subjected to pressure overload to assess cardiac remodeling.

Main Results:

  • Serum CCL21 levels were significantly higher in AS patients compared to controls.
  • Elevated CCL21 levels were independently associated with all-cause mortality in AS patients.
  • CCR7 was detected on macrophages, endothelial cells, and fibroblasts in human aortic valves.
  • Myocardial CCL21 and CCR7 expression increased in mice with LV pressure overload.
  • CCR7 knockout mice showed increased LV dilatation and reduced wall thickness after pressure overload.

Conclusions:

  • The CCL21/CCR7 signaling pathway appears to be implicated in the cardiac response to pressure overload secondary to aortic stenosis.
  • These findings suggest a potential therapeutic target for managing heart remodeling in AS.
Abstract

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