Viral and bacterial patterns induce TLR-mediated sustained XXXX and calcification in aortic valve interstitial cells.

@entity1 @entity32 @entity6800 @entity2939 @entity6801 @entity20040 @entity2938 @entity1435 @entity2071 @entity731 @entity472 @entity2247
BACKGROUND: @entity472 shares some ethiopathological features with @entity731 and increasing evidence links Toll-like receptors (TLRs) to atherogenesis. METHODS: TLR-mediated @entity32 and osteogenesis were investigated in @entity1 interstitial cells isolated from stenotic and non-stenotic aortic valves. TLR expression and signalling were evaluated by quantitative RT-PCR, flow cytometry, Western blot analysis, ELISA, and cytokine arrays. Osteogenesis was evaluated by measuring alkaline phosphatase activity. RESULTS: Interstitial cells from control valves express most TLRs, being @entity2939 the most abundant, whereas cells from stenotic valves express higher @entity2939 and @entity2938 and lower @entity20040 and @entity6801 transcript levels. When pro-inflammatory pathways were analyzed, we observed that @entity2939 , @entity2938 and @entity6800 ligands induced an early activation of NF-kB and @entity1435 MAPK activation in cells from control and stenotic valves. Strikingly, when TLRs sensing viral patterns were studied, a sustained @entity6800 -mediated activation of NF-kB, a kB-independent induction of catalytically active @entity2247 and @entity2071 expression, and induction of expression of several chemokines were observed. @entity2939 , but not @entity2938 , engagement produced a similar but NF-kB-dependent effect. Moreover, @entity6800 and @entity2939 agonists induced alkaline phosphatase expression and activity. CONCLUSIONS: Exposure of aortic valve interstitial cells to viral and Gram-negative bacteria molecular patterns induces distinct and long-term TLR-mediated pro-inflammatory and pro-osteogenic responses that might be relevant to the pathogenesis of @entity472 .
