Projects per year
Abstract / Description of output
Following myocardial infarction (MI), the adult heart has minimal regenerative potential. Conversely, the neonatal heart can undergo extensive regeneration, and neovascularization capacity was hypothesized to contribute to this difference. Here, we demonstrate the higher angiogenic potential of neonatal compared with adult mouse cardiac endothelial cells (MCECs) in vitro and use this difference to identify candidate microRNAs (miRs) regulating cardiac angiogenesis after MI. miR expression profiling revealed miR-96 and miR-183 upregulation in adult compared with neonatal MCECs. Their overexpression decreased the angiogenic potential of neonatal MCECs in vitro and prevented scar resolution and neovascularization in neonatal mice after MI. Inversely, their inhibition improved the angiogenic potential of adult MCECs, and miR-96/miR-183–KO mice had increased peri-infarct neovascularization. In silico analyses identified anillin (ANLN) as a direct target of miR-96 and miR-183. In agreement, Anln expression declined following their overexpression and increased after their inhibition in vitro. Moreover, ANLN expression inversely correlated with miR-96 expression and age in cardiac ECs of cardiovascular patients. In vivo, ANLN+ vessels were enriched in the peri-infarct area of miR-96/miR-183–KO mice. These findings identify miR-96 and miR-183 as regulators of neovascularization following MI and miR-regulated genes, such as anillin, as potential therapeutic targets for cardiovascular disease.
Original language | English |
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Article number | e134888 |
Journal | JCI Insight |
Volume | 5 |
Issue number | 14 |
Early online date | 16 Jun 2020 |
DOIs | |
Publication status | Published - 23 Jul 2020 |
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Dive into the research topics of 'Mir-96 and miR-183 differentially regulate neonatal and adult post-infarct neovascularisation'. Together they form a unique fingerprint.Projects
- 3 Finished
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BHF UK Cardiovascular Regenerative Medicine Centre
Newby, D., Brittan, M., Meloni, M., Mills, N. & Peault, B.
1/10/13 → 30/09/17
Project: Research
Equipment
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Edinburgh Preclinical Imaging
Carmel Moran (Manager), Adrian Thomson (Manager), Ross J Lennen (Manager), Adriana Tavares (Manager), Carlos J. Alcaide-Corral (Manager), Tim Morgan (Other), Islay Cranston (Other) & Kerry O'Rourke (Other)
Deanery of Clinical SciencesFacility/equipment: Facility