Journalartikel

Jahr der Veröffentlichung: 2020

Zeitschrift: International Journal of Molecular Sciences

Bandnummer: 21

Heftnummer: 23

eISSN: 1422-0067

Open Access Status: Gold

DOI Link: https://doi.org/10.3390/ijms21239099

Verlag: MDPI

Abstract: 
Although the response of the right ventricle (RV) to the increased afterload is an important determinant of the patient outcome, very little is known about the underlying mechanisms. Mast cells have been implicated in the pathogenesis of left ventricular maladaptive remodeling and failure. However, the role of mast cells in RV remodeling remains unexplored. We subjected mast cell-deficient WBB6F1-KitW/W-v (Kit(W)/Kit(W-v)) mice and their mast cell-sufficient littermate controls (MC+/+) to pulmonary artery banding (PAB). PAB led to RV dilatation, extensive myocardial fibrosis, and RV dysfunction in MC+/+ mice. In PAB Kit(W)/Kit(W-v) mice, RV remodeling was characterized by minimal RV chamber dilatation and preserved RV function. We further administered to C57Bl/6J mice either placebo or cromolyn treatment starting from day 1 or 7 days after PAB surgery to test whether mast cells stabilizing drugs can prevent or reverse maladaptive RV remodeling. Both preventive and therapeutic cromolyn applications significantly attenuated RV dilatation and improved RV function. Our study establishes 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 the heart.

Harvard-Zitierstil: Sydykov, A., Luitel, H., Mamazhakypov, A., Wygrecka, M., Pradhan, K., Pak, O., et al. (2020) Genetic Deficiency and Pharmacological Stabilization of Mast Cells Ameliorate Pressure Overload-Induced Maladaptive Right Ventricular Remodeling in Mice, International Journal of Molecular Sciences, 21(23), Article 9099. https://doi.org/10.3390/ijms21239099

APA-Zitierstil: Sydykov, A., Luitel, H., Mamazhakypov, A., Wygrecka, M., Pradhan, K., Pak, O., Petrovic, A., Kojonazarov, B., Weissmann, N., Seeger, W., Grimminger, F., Ghofrani, H., Kosanovic, D., & Schermuly, R. (2020). Genetic Deficiency and Pharmacological Stabilization of Mast Cells Ameliorate Pressure Overload-Induced Maladaptive Right Ventricular Remodeling in Mice. International Journal of Molecular Sciences. 21(23), Article 9099. https://doi.org/10.3390/ijms21239099