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. Author manuscript; available in PMC: 2022 Apr 30.
Published in final edited form as: Circ Res. 2021 Apr 29;128(9):1344–1370. doi: 10.1161/CIRCRESAHA.121.318011

Figure 5. Inflammatory pathway NFκB Modulates CAVD intracellularly and through cell-cell interactions.

Figure 5.

Bottom Right: NFκB activation in VIC through concerted efforts of inflammatory LPS/TLR signaling, LFA-1/ICAM-1 signaling, and Notch-1 signaling induces VIC osteoblastic differentiation and calcification. Left: Inflammation induces NFκB activation in VEC. NFκB+ VEC undergo EndMT, transforming into VIC (T-VIC). NFκB+ VEC have also been shown to exhibit evidence of osteoblastic differentiation. Knock-out of valve-specific NFκB in CAVD models prevents calcification and adverse valvular remodeling, consistent with the paradigm that NFκB activation in VEC promotes pathologic differentiation of VIC. Top right: Inflammatory cytokines TNFα and IL-6 activate NFκB signaling in VEC, which induces EndMT. It is unknown if Notch1 also plays a role in NFκB signaling in VEC. If so, Notch pathway could be a method through which VIC and VEC communicate in response to inflammation.