Release of leukotriene B4, transforming growth factor-beta1 and microparticles in relation to aortic valve calcification.

BACKGROUND AND AIM OF THE STUDY: Aortic stenosis, the most frequent valvulopathy in the Western world, is characterized by an important extracellular matrix (ECM) remodeling and a process of calcification in the aortic valves. One physiopathological assumption is that transforming growth factor-beta1 (TGF-beta1) acts through ECM remodeling and plays a role in calcification, implicating also microparticles (MPs). Another recent notion is the active involvement of inflammatory mediators in the calcification process of aortic stenosis.

METHODS: A total of 105 aortic valves was collected from patients suffering from calcified aortic stenosis with either tricuspid valve (AS) or bicuspid aortic valve (BAV), rheumatic aortic stenosis (RA), endocarditis, or aortic regurgitation (AR). Each valve was incubated for 24 h in culture medium and the supernatants (conditioned media) were used to measure the concentrations of leukotriene B4 (LTB4) and TGF-beta1 and to quantify the number of MPs released. Valvular calcification was evaluated using biphotonic absorptiometry.

RESULTS: LTB4 concentrations were significantly higher in media conditioned by AS valves compared to those conditioned by RA and endocarditis valves. In addition, LTB4 concentrations correlated significantly with the calcium content of the aortic valves. In contrast, the concentrations of TGF-beta1 and MPs in the conditioned media did not differ significantly between the various groups of valves, and there was no significant correlation between calcification and either TGF-beta1 or the number of MPs released from the aortic valves.

CONCLUSION: Taken together, these results indicate that inflammatory signaling through LTB4 may be more closely linked to calcification and aortic stenosis than signaling through TGF-beta1 and MPs.