Involvement of proinflammatory S100A9/A8 in the atherocalcinosis of aortic valves

Abstract

According to the results of the Euro-Heart Survey on Vascular Heart Disease the most common pathology is nonrheumatic aortic stenosis, it is also called as calcific aortic valve stenosis (CAVS), as in its pathogenesis the process of biomineralization of valve cusps and ring plays the main role. The aim of the work is the immunohistochemical study of mineralized tissue of aortic heart valves, which are affected by atherocalcinosis. Materials and methods. 30 samples of mineralized aortic valves (I group) and 10 samples of aortic valve without evidence of biomineralization (II group-control) were studied. Immunohistochemical study of expression of collagen (Collagen I), CD68, myeloperoxidase (MPO), calgranulin A (S100A8), calgranulin B (S100A9), caspase 3 (Casp 3) and osteopontin (OPN) was conducted in AV tissue of both groups. Results. In CAV tissues the fibrillar component (collagen I) growths was found, but the quantitative and qualitative compositions of CD68+ circulating inflammatory cells are not significantly different from the control group. CAVs contain much more MPO+-cells (p <0.001) in comparison to the group of AVs without biomineralization. Our data show a significant increase of the S100A9 and OPN expression in the mineralized tissue of AVs (p < 0.01). Also, a higher expression level of Casp3 and MPO was found in CAVs (p < 0.05). Comparing the first and the second groups of AVs connection between the expression of S100A8 was not determined. Conclusion. High Casp 3 expression confirms the increased level of cell elimination in the CAVs tissue, which is obviously connected with the impact of high local concentrations of S100A9. These facts can contribute to the development of pathological biomineralization of AV. Since osteopontin inhibits the hydroxyapatite formation by binding to the surface of the crystals, its hyperproduction is a counteracting factor against biomineralization in AV tissue.

Morphological and Crystal-Chemical Features of Macro- and Microcalcifications of Human Aorta

“…Generally, the IHC results converged with information about direct involvement of OPN in the formation and development of pathological biomineralization (Steiz et al, 2002;Moskalenko et al, 2017;Lok & Lyle, 2019). But, as we see here, the obvious role of OPN in the differentiation of macro-and microcalcifications of the atherosclerotic aorta has not been identified.…”

“…Primary antibodies against osteopontine (OPN; Invitrogen, PA5-34579, dilution 1:200) were used. Generally, immunohistochemical staining of tissue was performed according to the method, previously described in our works (Moskalenko et al, 2017). At least six different fields of view were analyzed for each sample.…”

Immunohistochemical Study of Ovarian Cancer With Pathological Biomineralization

“…Цей факт може свідчити про стимулювальний вплив біомінеральних депозитів на інтенсивність апоптозу у пухлинній тканині. Подібний вплив патологічної біомінералізації на процеси клітинної смерті в біомінералізованих тканинах був відмічений також в інших дослідженнях [20]. Цей феномен заслуговує на подальше більш детальне вивчення.…”