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 journalArticle

63 Citations (Scopus)

Abstract

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
Volume98
Issue number3
DOIs
StatePublished - Jun 1 2013

Fingerprint

Vascular Smooth Muscle
Smooth Muscle Myocytes
Cyclin D1
Phenotype
Carotid Arteries
Cell Dedifferentiation
Vascular System Injuries
Wounds and Injuries
Luciferases
MicroRNAs
Adenoviridae
Cell Proliferation
Apoptosis
Polymerase Chain Reaction
Messenger RNA
Proteins
In Vitro Techniques

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Merlet, E., Atassi, F., Motiani, R. K., Mougenot, N., Jacquet, A., Nadaud, S., ... Marchand, A. (2013). MiR-424/322 regulates vascular smooth muscle cell phenotype and neointimal formation in the rat. Cardiovascular Research, 98(3), 458-468. https://doi.org/10.1093/cvr/cvt045
Merlet, Elise ; Atassi, Fabrice ; Motiani, Rajender K. ; Mougenot, Nathalie ; Jacquet, Adeline ; Nadaud, Sophie ; Capiod, Thierry ; Trebak, Mohamed ; Lompré, Anne Marie ; Marchand, Alexandre. / MiR-424/322 regulates vascular smooth muscle cell phenotype and neointimal formation in the rat. In: Cardiovascular Research. 2013 ; Vol. 98, No. 3. pp. 458-468.
@article{296590cd906e4085a5a8ac652be02873,
title = "MiR-424/322 regulates vascular smooth muscle cell phenotype and neointimal formation in the rat",
abstract = "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.",
author = "Elise Merlet and Fabrice Atassi and Motiani, {Rajender K.} and Nathalie Mougenot and Adeline Jacquet and Sophie Nadaud and Thierry Capiod and Mohamed Trebak and Lompr{\'e}, {Anne Marie} and Alexandre Marchand",
year = "2013",
month = "6",
day = "1",
doi = "10.1093/cvr/cvt045",
language = "English (US)",
volume = "98",
pages = "458--468",
journal = "Cardiovascular Research",
issn = "0008-6363",
publisher = "Oxford University Press",
number = "3",

}

Merlet, E, Atassi, F, Motiani, RK, Mougenot, N, Jacquet, A, Nadaud, S, Capiod, T, Trebak, M, Lompré, AM & Marchand, A 2013, 'MiR-424/322 regulates vascular smooth muscle cell phenotype and neointimal formation in the rat', Cardiovascular Research, vol. 98, no. 3, pp. 458-468. https://doi.org/10.1093/cvr/cvt045

MiR-424/322 regulates vascular smooth muscle cell phenotype and neointimal formation in the rat. / Merlet, Elise; Atassi, Fabrice; Motiani, Rajender K.; Mougenot, Nathalie; Jacquet, Adeline; Nadaud, Sophie; Capiod, Thierry; Trebak, Mohamed; Lompré, Anne Marie; Marchand, Alexandre.

In: Cardiovascular Research, Vol. 98, No. 3, 01.06.2013, p. 458-468.

Research output: Contribution to journalArticle

TY - JOUR

T1 - MiR-424/322 regulates vascular smooth muscle cell phenotype and neointimal formation in the rat

AU - Merlet, Elise

AU - Atassi, Fabrice

AU - Motiani, Rajender K.

AU - Mougenot, Nathalie

AU - Jacquet, Adeline

AU - Nadaud, Sophie

AU - Capiod, Thierry

AU - Trebak, Mohamed

AU - Lompré, Anne Marie

AU - Marchand, Alexandre

PY - 2013/6/1

Y1 - 2013/6/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84877949558&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84877949558&partnerID=8YFLogxK

U2 - 10.1093/cvr/cvt045

DO - 10.1093/cvr/cvt045

M3 - Article

C2 - 23447642

AN - SCOPUS:84877949558

VL - 98

SP - 458

EP - 468

JO - Cardiovascular Research

JF - Cardiovascular Research

SN - 0008-6363

IS - 3

ER -