Angiotensin receptor blockers are associated with reduced fibrosis and interleukin-6 expression in calcific aortic valve disease

Pathobiology. 2014;81(1):15-24. doi: 10.1159/000350896. Epub 2013 Aug 21.

Abstract

Background: Calcific aortic valve disease (CAVD) is a chronic disorder characterized by the mineralization of the aortic valve and involving fibrosis.

Objectives: In this work we sought to determine if the fibrotic component of the remodeling process of CAVD was related to the use of angiotensin-converting enzyme inhibitors (ACEi) and/or angiotensin receptor blockers (ARBs).

Methods: In 477 patients with CAVD, the aortic valve was examined by histology. A semiquantitative score of fibrosis was generated and associations with clinical/cardiometabolic variables examined. In a subset of 103 patients the aortic valve was available to study the infiltration by inflammatory cells and expression of interleukin-6 (IL-6) by quantitative real-time PCR.

Results: The fibrosis score of the aortic valve was independently related to the hemodynamic severity of CAVD measured by echocardiography. The fibrotic score of the aortic valve was also related to the expression of IL-6. The use of ARBs but not of ACEi was associated with a lower fibrosis score of the aortic valve even after correction for covariates. In addition, patients under ARBs had lower aortic valve inflammation and expression of IL-6.

Conclusions: These findings suggest that ARBs may alter the fibrotic process of the aortic valve in CAVD, possibly by lowering tissue inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Angiotensin Receptor Antagonists / therapeutic use*
  • Aortic Valve / immunology
  • Aortic Valve / pathology
  • Bicuspid Aortic Valve Disease
  • Calcinosis / drug therapy*
  • Calcinosis / immunology
  • Calcinosis / pathology*
  • Female
  • Fibrosis
  • Heart Defects, Congenital / drug therapy*
  • Heart Defects, Congenital / immunology
  • Heart Defects, Congenital / pathology*
  • Heart Valve Diseases / drug therapy*
  • Heart Valve Diseases / immunology
  • Heart Valve Diseases / pathology*
  • Humans
  • Immunohistochemistry
  • Interleukin-6 / analysis
  • Interleukin-6 / biosynthesis*
  • Male
  • Real-Time Polymerase Chain Reaction

Substances

  • Angiotensin Receptor Antagonists
  • IL6 protein, human
  • Interleukin-6