MiR-424/322 regulates vascular smooth muscle cell phenotype and neointimal formation in the rat

Elise Merlet, Fabrice Atassi, Rajender K. Motiani, Nathalie Mougenot, Adeline Jacquet, Sophie Nadaud, Thierry Capiod, Mohamed Trebak, Anne Marie Lompré, Alexandre Marchand

Research output: Contribution to journalArticlepeer-review

98 Scopus citations


AimsOur aim was to identify new microRNAs (miRNAs) implicated in pathological vascular smooth muscle cells (VSMCs) proliferation and characterize their mechanism of action.Methods and resultsMicroRNAs microarray and qRT-PCR results lead us to focus on miR-424 or its rat ortholog miR-322 (miR-424/322). In vitro mir-424/322 level was decreased shortly after the induction of proliferation and increased in a time-dependent manner later on. In vivo its expression increased in the rat carotid artery from Day 4 up to Day 30 after injury. miR-424/322 overexpression in vitro inhibited proliferation and migration without affecting apoptosis and prevented VSMC dedifferentiation. Furthermore, miR-424/322 overexpression resulted in decreased expression of its predicted targets: cyclin D1 and Ca2+-regulating proteins calumenin and stromal-interacting molecule 1 (STIM1). Using reporter luciferase assays, we confirmed that cyclin D1 and calumenin mRNAs were direct targets of miR-322, whereas miR-322 effect on STIM1 was indirect. Nevertheless, consistent with the decreased STIM1 level, the store-operated Ca2+ entry was reduced. We hypothesized that miR-424/322 could be a negative regulator of proliferation overridden in pathological situations. Thus, we overexpressed miR-424/322 in injured rat carotid arteries using an adenovirus, and demonstrated a protective effect against restenosis.ConclusionOur results demonstrate that miR-424/322 is up-regulated after vascular injury. This is likely an adaptive response to counteract proliferation, although this mechanism is overwhelmed in pathological situations such as injury-induced restenosis.

Original languageEnglish (US)
Pages (from-to)458-468
Number of pages11
JournalCardiovascular Research
Issue number3
StatePublished - Jun 1 2013

All Science Journal Classification (ASJC) codes

  • General Medicine


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