Mononuclear cell infiltration in valvular tissue is one of the characteristics in calcific aortic valve disease. The inflammatory responses of aortic valve interstitial cells (AVICs) play an important role in valvular inflammation. However, it remains unclear what may evoke AVIC inflammatory responses. Accumulation of biglycan has been found in diseased aortic valve leaflets. Soluble biglycan can function as a danger-associated molecular pattern to induce the production of proinflammatory mediators in cultured macrophages. We tested the hypothesis that soluble biglycan induces AVIC production of proinflammatory mediators involved in mononuclear cell infiltration through Toll-like receptor (TLR)-dependent signaling pathways.