Share this page on LinkedIn
Share This Page on Google+
Share This Page on Twitter
tell someone about this page print this page
You are here: Contents > 2012 > Volume 21 Number 1 January 2012 > AORTIC VALVE DISEASE > Tezosentan Inhibits Uptake of Proinflammatory Endothelin-1 in Stenotic Aortic Valves

Tezosentan Inhibits Uptake of Proinflammatory Endothelin-1 in Stenotic Aortic Valves

Hannu-Ville Leskelä, Olli Vuolteenaho, Marja-Kaisa Koivula, Panu Taskinen, Heikki Ruskoaho, Tuomas Peltonen, Petri Lehenkari 

Institute of Biomedicine, Department of Anatomy, University of Oulu, Surgery Clinic, Oulu University Hospital, Institute of Biomedicine, Department of Physiology, Biocenter Oulu, University of Oulu, Institute of Diagnostics, Department of Clinical Chemistry, University of Oulu, Department of Cardiovascular Surgery, Oulu University Hospital, Institute of Biomedicine, Department of Pharmacology and Toxicology, Biocenter Oulu, University of Oulu, Finland

Background and aim of the study: Aortic valve stenosis (AS) is an actively regulated pathobiological process which has an inflammation origin, and manifests as an accumulation of lipids and, ultimately, calcification of the aortic valve tissue. Increased plasma levels of the proinflammatory factor endothelin-1 (ET-1) have been reported in AS. Moreover, increased tissue levels of ET-1 and its ETA receptor, which mediates the fibrotic and proliferative effects of ET-1, have been reported in stenotic aortic valves. The study aim was to determine whether endothelin receptor antagonism has an effect on the supposed receptor-mediated uptake of ET-1 to aortic valves when ET-1 may be involved in the pathogenesis of AS.
Methods: By using valve tissue explants in culture, it was determined whether the ETA-ETB receptor antagonist tezosentan was capable of reducing the uptake of 125I-labeled ET-1 to human aortic valves. Aortic valves were obtained from 16 patients (11 males, five females; mean age 71 ± 11.2 years) and

from two donors without AS (as controls) at the time of aortic valve or aortic root surgery. Valve tissue samples were cultured in ET-1 (10 nmol/l), in the presence or absence of tezosentan (10 nmol/l).
Results: ET-1 uptake was found to be pronounced in the calcified areas of the valve, and tezosentan markedly reduced the receptor-mediated uptake of 125I-labeled ET-1. The inhibitory effect was most
evident in the well-calcified part of the valve. The gene expression levels of the ET receptors ETA and ETB were unaltered in human aortic valves during a four-day exposure to the antagonist.
Conclusion: The ability of the ETA-ETB receptor antagonist tezosentan to inhibit ET-1 uptake in valve tissue suggests that continuous ET antagonist
therapy might serve as new strategy to slow down the pathophysiological processes of AS.



The Journal of Heart Valve Disease 2012;21:23-30

Tezosentan Inhibits Uptake of Proinflammatory Endothelin-1 in Stenotic Aortic Valves

Click the above hyperlink to view the article, right click (Ctrl click on a Mac) to open in a new browser window or tab.

Purchase this Article

This article doesn't appear to be availble for purchase as a single artilce. Please contact us for further information.