biostudies-literatureTierney JWNIDDK NIH HHSNHLBI NIH HHSNational Institute of HealthNCI NIH HHSNIGMS NIH HHSNIH HHSNational Science Foundatione142339https://www.ebi.ac.uk/biostudies/studies/S-EPMC8525639biostudies-literatureUnknown6(19)Vascular procedures, such as stenting, angioplasty, and bypass grafting, often fail due to intimal hyperplasia (IH), wherein contractile vascular smooth muscle cells (VSMCs) dedifferentiate to synthetic VSMCs, which are highly proliferative, migratory, and fibrotic. Previous studies suggest MAPK-activated protein kinase 2 (MK2) inhibition may limit VSMC proliferation and IH, although the molecular mechanism underlying the observation remains unclear. We demonstrated here that MK2 inhibition blocked the molecular program of contractile to synthetic dedifferentiation and mitigated IH development. Molecular markers of the VSMC contractile phenotype were sustained over time in culture in rat primary VSMCs treated with potent, long-lasting MK2 inhibitory peptide nanopolyplexes (MK2i-NPs), a resJCI insightTherapeutic MK2 inhibition blocks pathological vascular smooth muscle cell phenotype switch.PMC8525639T32 GM152284S10 OD023475STTR 1622828P30 CA068485U24 DK059637R01HL122347,T32GM007347T32 GM007347R01 HL122347Colazo JMCook RSDuvall CLCheung-Flynn JEvans BCWang BBrophy CMPolcz METierney JWfalseTherapeutic MK2 inhibition blocks pathological vascular smooth muscle cell phenotype switch.Vascular procedures, such as stenting, angioplasty, and bypass grafting, often fail due to intimal hyperplasia (IH), wherein contractile vascular smooth muscle cells (VSMCs) dedifferentiate to synthetic VSMCs, which are highly proliferative, migratory, and fibrotic. Previous studies suggest MAPK-activated protein kinase 2 (MK2) inhibition may limit VSMC proliferation and IH, although the molecular mechanism underlying the observation remains unclear. We demonstrated here that MK2 inhibition blocked the molecular program of contractile to synthetic dedifferentiation and mitigated IH development. Molecular markers of the VSMC contractile phenotype were sustained over time in culture in rat primary VSMCs treated with potent, long-lasting MK2 inhibitory peptide nanopolyplexes (MK2i-NPs), a res2021-01-01T00:00:00Z2021 Oct2026-05-08T15:50:27.716Z2025-02-19T00:03:06.012ZS-EPMC85256393462280310.1172/jci.insight.142339