TNF and calcification: In calcified aortic valves, more monocytes infiltrate into the tissue to differentiate into pro-inflammatory macrophages, which secret inflammatory cytokines such as IL-6 and TNF-α, promoting AVICs activation and inducing alkaline phosphatase expression, eventually leading to aortic valvular calcification (Kaden et al., 2005; Lee and Choi, 2016).