Over-expression of neurotrophin 3 in human aortic valves affected by calcific disease induces the osteogenic responses via the Trk-Akt pathway.

摘要: Abstract Calcific aortic valve disease (CAVD) is a leading cardiovascular disorder in the elderly. While interstitial cells (AVICs) are main that express osteogenic mediators, molecular mechanism mediates AVIC responses incompletely understood. This study aims to identify pro-osteogenic factors human AVICs affected by CAVD. Methods and results Microarray analysis identified 11 up-regulated genes of diseased valves. Among these genes, mRNA levels neurotrophin 3 (NT3) increased 2 fold. Higher NT3 protein valves were confirmed immunofluorescent staining immunoblotting, respectively. An exposure normal recombinant (0.025–0.10 μg/mL) production Runx2, TGF-β1 BMP-2 dose-dependent fashion. also promotes calcium deposit formation. The effect was not neutralization Toll-like receptor or 4. Interestingly, encoding neural growth factor receptors (TrkA, TrkB, TrkC p75 NTR) detectable AVICs. Inhibition Trk markedly reduced effects on production, formation Akt phosphorylation. Further, inhibition NT3. Conclusions higher up-regulates BMP-2, via Trk–Akt pathway. Thus, novel may play role valvular calcification.