Affordable Access

Publisher Website

Induction of local angiotensin II-producing systems in stenotic aortic valves

Authors
Journal
Journal of the American College of Cardiology
0735-1097
Publisher
Elsevier
Publication Date
Volume
44
Issue
9
Identifiers
DOI: 10.1016/j.jacc.2004.07.054
Disciplines
  • Biology
  • Chemistry
  • Medicine

Abstract

Objectives The purpose of this study was to investigate the expression of angiotensin II (Ang II)-producing enzyme systems in normal and stenotic aortic valves. Background Chronic inflammation and fibrosis are involved in the pathogenesis of aortic stenosis (AS), but the detailed molecular mechanisms of this atherosclerosis-like process remain obscure. Angiotensin II, a powerful mediator of inflammation and fibrosis, may participate in AS progression. Methods Stenotic aortic valves (n = 86) were obtained from patients undergoing valve replacement surgery, and control valves (n = 11) were obtained from patients undergoing cardiac transplantation. Angiotensin-converting enzyme (ACE) and mast cell (MC)-derived chymase were quantified by reverse-transcription polymerase chain reaction, autoradiography, and immunostaining. The MCs, macrophages, and T lymphocytes were detected by immunohistochemistry, and angiotensin II type 1 receptor (AT-1R) by autoradiography. Results Compared with control valves, stenotic aortic valves showed a significant increase in both messenger ribonucleic acid (mRNA) (p = 0.001) and protein (p < 0.001) expression of ACE, which colocalized with macrophages. Similarly, the expression of AT-1R protein and chymase mRNA and proteinwas upregulated (p < 0.001), and the number of MCs was six-fold higher in stenotic than in normal valves. The MCs were associated with the calcified areas, and—in contrast to control valves—showed an increased degree of degranulation, a prerequisite for chymase secretion and action. Conclusions Angiotensin-converting enzyme and chymase, two Ang II-forming enzymes, are locally expressed in aortic valves, and owing to infiltration of macrophages and MCs, are further upregulated in stenotic valves. These novel findings, implicating chronic inflammation and an increased expression of local Ang II-forming systems, suggest that therapeutic interventions aiming at inhibiting these processes may slow AS progression.

There are no comments yet on this publication. Be the first to share your thoughts.

Statistics

Seen <100 times
0 Comments

More articles like this

Induction of local angiotensin II-producing system...

on Journal of the American Colleg... Nov 02, 2004

Angiotensin receptor blockers are associated with...

on European Journal of Clinical I... November 2011

Retrograde crossing of stenotic aortic valves.

on Catheterization and cardiovasc... March 1991

Morphology of critically stenotic aortic valves.

on Journal of Thoracic and Cardio... August 1995
More articles like this..