Role of mast cells in pressure overload induced right ventricular remodeling and failure
Cardiology, Angiology
Final Report Abstract
Taken together, we demonstrated a previously undescribed role of mast cells in pressure overload-induced adverse RV remodeling. Mast cells may thus represent an interesting target for the development of a new therapeutic approach directed specifically at right ventricle. Mast cells store various proteases and a wide variety of mediators. Furthermore, mast cells are multi-functional cells capable of overwhelming as well as discrete responses. In our project, we investigated effects of genetic deficiency of mast cells, pharmacological stabilization of mast cell membrane and mast cell chymase deficiency and inhibition. Most prominent effects on the RV remodeling were achieved by mast cell deficiency suggesting a potential contribution of other mediators into the pressure overload-induced RV remodeling. Indeed, pharmacological mast cell stabilization only prevents calcium-dependent mast cell degranulation, but mast cell secretion of mediators independently of degranulation is not inhibited. Therefore, it might be interesting to investigate the role of many individual mediators secreted by mast cells by selective mast cell-specific inactivation of their genes using Mcpt5-Cre transgenic mice.
Publications
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Pressure overload leads to an increased accumulation and activity of mast cells in the right ventricle. Physiol Rep. 2017 Mar;5(6). pii: e13146
Luitel H, Sydykov A, Schymura Y, Mamazhakypov A, Janssen W, Pradhan K, Wietelmann A, Kosanovic D, Dahal BK, Weissmann N, Seeger W, Grimminger F, Ghofrani HA, Schermuly RT
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Inflammatory mediators drive adverse right ventricular remodeling and dysfunction and serve as potential biomarkers. Front Physiol. 2018 May 23;9:609
Sydykov A, Mamazhakypov A, Petrovic A, Kosanovic D, Sarybaev AS, Weissmann N, Ghofrani HA, Schermuly RT
