Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Murtha, LA; Hardy, SA; Mabotuwana, NS; Bigland, MJ; Bailey, T; Raguram, K; Liu, SF; Ngo, DT; Sverdlov, AL; Tomin, T; Birner-Gruenberger, R; Hume, RD; Iismaa, SE; Humphreys, DT; Patrick, R; Chong, JJH; Lee, RJ; Harvey, RP; Graham, RM; Rainer, PP; Boyle, AJ.
Fibulin-3 is necessary to prevent cardiac rupture following myocardial infarction
SCI REP-UK. 2023; 13(1): 14995
Doi: 10.1038/s41598-023-41894-9
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- Co-Autor*innen der Med Uni Graz
- Birner-Grünberger Ruth
- Rainer Peter
- Tomin Tamara
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- Abstract:
- 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 similar to 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.