Increased Infiltration of Extra-Cardiac Cells in Myxomatous Valve Disease
Mutations in the actin-binding gene Filamin-A have been linked to non-syndromic myxomatous valvular dystrophy and associated mitral valve prolapse. Previous studies by our group traced the adult valve defects back to developmental errors in valve interstitial cell-mediated extracellular matrix remod...
Main Authors: | , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2015-07-01
|
Series: | Journal of Cardiovascular Development and Disease |
Subjects: | |
Online Access: | http://www.mdpi.com/2308-3425/2/3/200 |
id |
doaj-6f0cef17ec8440c9bfe5c058f1a7d8be |
---|---|
record_format |
Article |
spelling |
doaj-6f0cef17ec8440c9bfe5c058f1a7d8be2020-11-24T21:25:48ZengMDPI AGJournal of Cardiovascular Development and Disease2308-34252015-07-012320021310.3390/jcdd2030200jcdd2030200Increased Infiltration of Extra-Cardiac Cells in Myxomatous Valve DiseaseKimberly Sauls0Katelynn Toomer1Katherine Williams2Amanda J. Johnson3Roger R. Markwald4Zoltan Hajdu5Russell A. Norris6Department of Regenerative Medicine and Cell Biology, Children's Research Institute, Medical University of South Carolina, 171 Ashley Ave, Charleston, SC 29425, USADepartment of Regenerative Medicine and Cell Biology, Children's Research Institute, Medical University of South Carolina, 171 Ashley Ave, Charleston, SC 29425, USADepartment of Regenerative Medicine and Cell Biology, Children's Research Institute, Medical University of South Carolina, 171 Ashley Ave, Charleston, SC 29425, USADepartment of Regenerative Medicine and Cell Biology, Children's Research Institute, Medical University of South Carolina, 171 Ashley Ave, Charleston, SC 29425, USADepartment of Regenerative Medicine and Cell Biology, Children's Research Institute, Medical University of South Carolina, 171 Ashley Ave, Charleston, SC 29425, USADepartment of Bioengineering, Clemson University, 200 C Patewood Drive, Greenville, SC 29615, USADepartment of Regenerative Medicine and Cell Biology, Children's Research Institute, Medical University of South Carolina, 171 Ashley Ave, Charleston, SC 29425, USAMutations in the actin-binding gene Filamin-A have been linked to non-syndromic myxomatous valvular dystrophy and associated mitral valve prolapse. Previous studies by our group traced the adult valve defects back to developmental errors in valve interstitial cell-mediated extracellular matrix remodeling during fetal valve gestation. Mice deficient in Filamin-A exhibit enlarged mitral leaflets at E17.5, and subsequent progression to a myxomatous phenotype is observed by two months. For this study, we sought to define mechanisms that contribute to myxomatous degeneration in the adult Filamin-A-deficient mouse. In vivo experiments demonstrate increased infiltration of hematopoietic-derived cells and macrophages in adolescent Filamin-A conditional knockout mice. Concurrent with this infiltration of hematopoietic cells, we show an increase in Erk activity, which localizes to regions of MMP2 expression. Additionally, increases in cell proliferation are observed at two months, when hematopoietic cell engraftment and signaling are pronounced. Similar changes are observed in human myxomatous mitral valve tissue, suggesting that infiltration of hematopoietic-derived cells and/or increased Erk signaling may contribute to myxomatous valvular dystrophy. Consequently, immune cell targeting and/or suppression of pErk activities may represent an effective therapeutic option for mitral valve prolapse patients.http://www.mdpi.com/2308-3425/2/3/200Filamin-Amyxomatous valve diseasehematopoietic cellsmacrophage |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Kimberly Sauls Katelynn Toomer Katherine Williams Amanda J. Johnson Roger R. Markwald Zoltan Hajdu Russell A. Norris |
spellingShingle |
Kimberly Sauls Katelynn Toomer Katherine Williams Amanda J. Johnson Roger R. Markwald Zoltan Hajdu Russell A. Norris Increased Infiltration of Extra-Cardiac Cells in Myxomatous Valve Disease Journal of Cardiovascular Development and Disease Filamin-A myxomatous valve disease hematopoietic cells macrophage |
author_facet |
Kimberly Sauls Katelynn Toomer Katherine Williams Amanda J. Johnson Roger R. Markwald Zoltan Hajdu Russell A. Norris |
author_sort |
Kimberly Sauls |
title |
Increased Infiltration of Extra-Cardiac Cells in Myxomatous Valve Disease |
title_short |
Increased Infiltration of Extra-Cardiac Cells in Myxomatous Valve Disease |
title_full |
Increased Infiltration of Extra-Cardiac Cells in Myxomatous Valve Disease |
title_fullStr |
Increased Infiltration of Extra-Cardiac Cells in Myxomatous Valve Disease |
title_full_unstemmed |
Increased Infiltration of Extra-Cardiac Cells in Myxomatous Valve Disease |
title_sort |
increased infiltration of extra-cardiac cells in myxomatous valve disease |
publisher |
MDPI AG |
series |
Journal of Cardiovascular Development and Disease |
issn |
2308-3425 |
publishDate |
2015-07-01 |
description |
Mutations in the actin-binding gene Filamin-A have been linked to non-syndromic myxomatous valvular dystrophy and associated mitral valve prolapse. Previous studies by our group traced the adult valve defects back to developmental errors in valve interstitial cell-mediated extracellular matrix remodeling during fetal valve gestation. Mice deficient in Filamin-A exhibit enlarged mitral leaflets at E17.5, and subsequent progression to a myxomatous phenotype is observed by two months. For this study, we sought to define mechanisms that contribute to myxomatous degeneration in the adult Filamin-A-deficient mouse. In vivo experiments demonstrate increased infiltration of hematopoietic-derived cells and macrophages in adolescent Filamin-A conditional knockout mice. Concurrent with this infiltration of hematopoietic cells, we show an increase in Erk activity, which localizes to regions of MMP2 expression. Additionally, increases in cell proliferation are observed at two months, when hematopoietic cell engraftment and signaling are pronounced. Similar changes are observed in human myxomatous mitral valve tissue, suggesting that infiltration of hematopoietic-derived cells and/or increased Erk signaling may contribute to myxomatous valvular dystrophy. Consequently, immune cell targeting and/or suppression of pErk activities may represent an effective therapeutic option for mitral valve prolapse patients. |
topic |
Filamin-A myxomatous valve disease hematopoietic cells macrophage |
url |
http://www.mdpi.com/2308-3425/2/3/200 |
work_keys_str_mv |
AT kimberlysauls increasedinfiltrationofextracardiaccellsinmyxomatousvalvedisease AT katelynntoomer increasedinfiltrationofextracardiaccellsinmyxomatousvalvedisease AT katherinewilliams increasedinfiltrationofextracardiaccellsinmyxomatousvalvedisease AT amandajjohnson increasedinfiltrationofextracardiaccellsinmyxomatousvalvedisease AT rogerrmarkwald increasedinfiltrationofextracardiaccellsinmyxomatousvalvedisease AT zoltanhajdu increasedinfiltrationofextracardiaccellsinmyxomatousvalvedisease AT russellanorris increasedinfiltrationofextracardiaccellsinmyxomatousvalvedisease |
_version_ |
1725982585955287040 |