Mir-96 and miR-183 differentially regulate neonatal and adult post-infarct neovascularisation

Raphael F.p. Castellan, Milena Vitiello, Martina Vidmar, Steven Johnstone, Dominga Iacobazzi, David Mellis, Benjamin Cathcart, Adrian Jw Thomson, Christiana Ruhrberg, Massimo Caputo, David E. Newby, Gillian A. Gray, Andrew Howard Baker, Andrea Caporali, Marco Meloni

Research output: Contribution to journalArticlepeer-review

Abstract

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 languageEnglish
Article numbere134888
Journal JCI Insight
Volume5
Issue number14
Early online date16 Jun 2020
DOIs
Publication statusPublished - 23 Jul 2020

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