Involvement of Immune Cell Network in Aortic Valve Stenosis: Communication between Valvular Interstitial Cells and Immune Cells

Abstract

Aortic valve stenosis is a heart disease prevalent in the elderly characterized by valvular calcification, fibrosis, and inflammation, but its exact pathogenesis remains unclear. Previously, aortic valve stenosis was thought to be caused by chronic passive and degenerative changes associated with aging. However, recent studies have demonstrated that atherosclerotic processes and inflammation can induce valvular calcification and bone deposition, leading to valvular stenosis. In particular, the most abundant cell type in cardiac valves, valvular interstitial cells, can differentiate into myofibroblasts and osteoblast-like cells, leading to valvular calcification and stenosis. Differentiation of valvular interstitial cells can be trigged by inflammatory stimuli from several immune cell types, including macrophages, dendritic cells, T cells, B cells, and mast cells. This review indicates that crosstalk between immune cells and valvular interstitial cells plays an important role in the development of aortic valve stenosis.

Morinda citrifolia noni water extract enhances innate and adaptive immune responses in healthy mice, ex vivo, and in vitro

“…As Figure 1e shows, there was no shape change of RAW264.7 cells compared with normal group, as shown in the case of ginseng-derived acid polysaccharides but not LPS, implying that the activation of macrophages is different from that of LPS/TLR4induced activation conditions. Consistent with previous papers (Hirazumi & Furusawa, 1999;Nayak & Mengi, 2009;Palu et al, 2008), This results in the activation of inflammatory signaling pathways, such as those initiated by nuclear factor-kappa B (NF-κB) and activator protein-1 (AP-1; Lee & Choi, 2016;Yang et al, 2014;Yi et al, 2014). Therefore, we examined the effect of Mc-eWE on the activation of intracellular signaling kinases and transcription factors in both the NF-κB and AP-1 pathways, using Western blot analyses.…”

“…Stimulation of macrophages initiates intracellular signaling cascades through a number of signaling kinases. This results in the activation of inflammatory signaling pathways, such as those initiated by nuclear factor‐kappa B (NF‐κB) and activator protein‐1 (AP‐1; Lee & Choi, ; Yang et al, ; Yi et al, ). Therefore, we examined the effect of Mc‐eWE on the activation of intracellular signaling kinases and transcription factors in both the NF‐κB and AP‐1 pathways, using Western blot analyses.…”

Interleukin-37 suppresses the osteogenic responses of human aortic valve interstitial cells in vitro and alleviates valve lesions in mice

“…Inflammatory mediators promote valvular osteogenic responses and are believed to contribute to the mechanism for the pathogenesis of CAVD (2,3). Aortic valve interstitial cells (AVICs), the dominant cellular components of aortic valve leaflets, play a critical role in aortic valve inflammation and calcification (4,5). In this regard, proinflammatory mediators, such as tumor necrosis factor-α, have been shown to up-regulate the expression of osteogenic factor bone morphogenetic protein-2 (BMP-2) and early osteoblastic differentiation biomarker alkaline phosphatase (ALP) in AVICs (6, 7).…”

Activation of the calcium-sensing receptor in human valvular interstitial cells promotes calcification

“…Calcific aortic valve disease was long considered to be a passive degenerative condition. However, it is now conceptualized as a more complex, actively regulated disease process [10] that results from a phenotypic switch of quiescent valvular interstitial cells to a myofibroblast-like phenotype and then an osteoblast-like phenotype [11]. Heart valves contain a heterogeneous population of valvular endothelial cells and valvular interstitial cells (VICs), which maintain valve homeostasis and leaflet integrity.…”

“…It is noteworthy that VICs in calcified valves may also display an osteogenic phenotype, with enhanced expression of osteoblast markers like runt-related transcription factor 2 (Runx2), osterix (Osx), Bmp2, and osteopontin (Opn) [12,13]. The osteoblast-like activity of these VICs is thought to be responsible for the mineralization process associated with CAVD [11,14]. However, the exact cellular and molecular pathways of CAVD initiation and progression remain poorly understood.…”