- Title
- Fibulin-3 is necessary to prevent cardiac rupture following myocardial infarction
- Creator
- Murtha, Lucy A.; Hardy, Sean A.; Birner-Gruenberger, Ruth; Hume, Robert D.; Iismaa, Siiri E.; Humphreys, David T.; Patrick, Ralph; Chong, James J. H.; Lee, Randall J.; Harvey, Richard P.; Graham, Robert M.; Rainer, Peter P.; Mabotuwana, Nishani S.; Boyle, Andrew J.; Bigland, Mark J.; Bailey, Taleah; Raguram, Kalyan; Liu, Saifei; Ngo, Doan T.; Sverdlov, Aaron L.; Tomin, Tamara
- Relation
- Scientific Reports Vol. 13, no. 14995
- Publisher Link
- http://dx.doi.org/10.1038/s41598-023-41894-9
- Publisher
- Nature Publishing Group
- Resource Type
- journal article
- Date
- 2023
- Description
- Despite the high prevalence of heart failure in the western world, there are few effective treatments. Fibulin-3 is a protein involved in extracellular matrix (ECM) structural integrity, however its role in the heart is unknown. We have demonstrated, using single cell RNA-seq, that fibulin-3 was highly expressed in quiescent murine cardiac fibroblasts, with expression highest prior to injury and late post-infarct (from ~ day-28 to week-8). In humans, fibulin-3 was upregulated in left ventricular tissue and plasma of heart failure patients. Fibulin-3 knockout (Efemp1 −/−) and wildtype mice were subjected to experimental myocardial infarction. Fibulin-3 deletion resulted in significantly higher rate of cardiac rupture days 3–6 post-infarct, indicating a weak and poorly formed scar, with severe ventricular remodelling in surviving mice at day-28 post-infarct. Fibulin-3 knockout mice demonstrated less collagen deposition at day-3 post-infarct, with abnormal collagen fibre-alignment. RNA-seq on day-3 infarct tissue revealed upregulation of ECM degradation and inflammatory genes, but downregulation of ECM assembly/structure/organisation genes in fibulin-3 knockout mice. GSEA pathway analysis showed enrichment of inflammatory pathways and a depletion of ECM organisation pathways. Fibulin-3 originates from cardiac fibroblasts, is upregulated in human heart failure, and is necessary for correct ECM organisation/structural integrity of fibrotic tissue to prevent cardiac rupture post-infarct.
- Subject
- heart failure; Fibulin-3; cardiac fibroblasts; fibrotic tissue
- Identifier
- http://hdl.handle.net/1959.13/1488401
- Identifier
- uon:52438
- Identifier
- ISSN:2045-2322
- Rights
- x
- Language
- eng
- Reviewed
- Hits: 4513
- Visitors: 4492
- Downloads: 0
| Thumbnail | File | Description | Size | Format |
|---|