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Regulation of Cardiac Mast Cell Maturation and Function by the Neurokinin-1 Receptor in the Fibrotic Heart
- Source :
- Scientific Reports, Vol 9, Iss 1, Pp 1-11 (2019), Scientific Reports
- Publication Year :
- 2019
- Publisher :
- Nature Publishing Group, 2019.
-
Abstract
- 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.
- Subjects :
- Male
0301 basic medicine
medicine.medical_specialty
Cardiac fibrosis
lcsh:Medicine
Heart failure
Apoptosis
Rats, Inbred WKY
Article
Mice
03 medical and health sciences
0302 clinical medicine
Fibrosis
Rats, Inbred SHR
Internal medicine
Tachykinin receptor 1
Renin–angiotensin system
medicine
Animals
Mast Cells
Receptor
lcsh:Science
Multidisciplinary
business.industry
Myocardium
lcsh:R
3T3 Cells
Fibroblasts
Receptors, Neurokinin-1
medicine.disease
Mast cell
Angiotensin II
3. Good health
Mice, Inbred C57BL
Cardiac hypertrophy
030104 developmental biology
Endocrinology
medicine.anatomical_structure
Hypertension
lcsh:Q
business
030217 neurology & neurosurgery
Subjects
Details
- Language :
- English
- ISSN :
- 20452322
- Volume :
- 9
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Scientific Reports
- Accession number :
- edsair.doi.dedup.....776edef61f5a8335987be3341c4c3c2e