Regulation of Cardiac Mast Cell Maturation and Function by the Neurokinin-1 Receptor in the Fibrotic Heart.

Autor: Widiapradja A; Kolling Institute of Medical Research, Royal North Shore Hospital, St Leonards, NSW, 2065, Australia.; Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW, 2006, Australia., Manteufel EJ; Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, WI, 53226, USA., Dehlin HM; Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, WI, 53226, USA., Pena J; Department of Physiology, Medical College of Wisconsin, Milwaukee, WI, 53226, USA., Goldspink PH; Department of Physiology, Medical College of Wisconsin, Milwaukee, WI, 53226, USA., Sharma A; Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, WI, 53226, USA., Kolb LL; Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, WI, 53226, USA., Imig JD; Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, WI, 53226, USA., Janicki JS; Cell Biology and Anatomy, University of South Carolina School of Medicine, Columbia, SC, 29208, USA., Lu B; Division of Respiratory Diseases, Boston Children's Hospital, Harvard Medical School, Boston, MA, 02115, USA., Levick SP; Kolling Institute of Medical Research, Royal North Shore Hospital, St Leonards, NSW, 2065, Australia. scott.levick@sydney.edu.au.; Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW, 2006, Australia. scott.levick@sydney.edu.au.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2019 Jul 29; Vol. 9 (1), pp. 11004. Date of Electronic Publication: 2019 Jul 29.
DOI: 10.1038/s41598-019-47369-0
Abstrakt: Cardiac fibrosis is an underlying cause of diastolic dysfunction, contributing to heart failure. Substance P (SP) activation of the neurokinin-1 receptor (NK-1R) contributes to cardiac fibrosis in hypertension. However, based on in vitro experiments, this does not appear to be via direct activation of cardiac fibroblasts. While numerous cells could mediate the fibrotic effects of SP, herein, we investigate mast cells (MC) as a mechanism mediating the fibrotic actions of SP, since MCs are known to play a role in cardiac fibrosis and respond to SP. Spontaneously hypertensive rats (SHR) were treated with the NK-1R antagonist L732138 (5 mg/kg/d) from 8 to 12 weeks of age. L732138 prevented increased MC maturation of resident immature MCs. NK-1R blockade also prevented increased cardiac MC maturation in angiotensin II-infused mice. MC-deficient mice were used to test the importance of MC NK-1Rs to MC activation. MC-deficient mice administered angiotensin II did not develop fibrosis; MC-deficient mice reconstituted with MCs did develop fibrosis. MC-deficient mice reconstituted with MCs lacking the NK-1R also developed fibrosis, indicating that NK-1Rs are not required for MC activation in this setting. In conclusion, the NK-1R causes MC maturation, however, other stimuli are required to activate MCs to cause fibrosis.
Databáze: MEDLINE
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