Castellan, RF;
Vitiello, M;
Vidmar, M;
Johnstone, S;
Iacobazzi, D;
Mellis, D;
Cathcart, B;
... Meloni, M; + view all
(2020)
Mir-96 and miR-183 differentially regulate neonatal and adult post-infarct neovascularisation.
JCI Insight
10.1172/jci.insight.134888.
(In press).
Preview |
Text
134888.1-20200612102930-covered-253bed37ca4c1ab43d105aefdf7b5536.pdf - Accepted Version Download (10MB) | Preview |
Abstract
Following myocardial infarction (MI), the adult heart has minimal regenerative potential. Conversely, the neonatal heart can undergo extensive regeneration, and neovascularisation capacity was hypothesised to contribute to this difference. Here, we demonstrate the higher angiogenic potential of neonatal compared to 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 to neonatal MCECs. Their overexpression decreased the angiogenic potential of neonatal MCECs in vitro and prevented scar resolution and neovascularisation in neonatal mice after MI. Inversely, their inhibition improved the angiogenic potential of adult MCECs, and miR-96/miR-183 knock-out mice had increased peri-infarct neovascularisation. 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-positive vessels were enriched in the peri-infarct area of miR-96/miR-183 knock-out mice. These findings identify miR-96 and miR-183 as regulators of neovascularisation following MI and miR-regulated genes such as anillin as potential therapeutic targets for cardiovascular disease.
| Type: | Article |
|---|---|
| Title: | Mir-96 and miR-183 differentially regulate neonatal and adult post-infarct neovascularisation |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1172/jci.insight.134888 |
| Publisher version: | https://doi.org/10.1172/jci.insight.134888 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Angiogenesis, Cardiovascular disease, Vascular Biology |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10102349 |
Archive Staff Only
 |
View Item |
