ArticleJournal of vascular surgery2010
A novel cell permeant peptide inhibitor of MAPKAP kinase II inhibits intimal hyperplasia in a human saphenous vein organ culture model.
Article in Journal of vascular surgery, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 23 citations in OpenAlex.
- Nanomedicine-based strategies for the treatment of vein graft disease.Nature reviews. Cardiology · 2025Review
- Therapeutic MK2 inhibition blocks pathological vascular smooth muscle cell phenotype switch.JCI insight · 2021Article
- Nanotechnology Enabled Modulation of Signaling Pathways Affects Physiologic Responses in Intact Vascular Tissue.Tissue engineering. Part A · 2019Article
- Cell penetrating peptides: a comparative transport analysis for 474 sequence motifs.Drug delivery · 2018Article
- Non-alcoholic fatty liver disease phosphoproteomics: A functional piece of the precision puzzle.Hepatology research : the official journal of the Japan Society of Hepatology · 2017Article
- Heparin-functionalized polymer graft surface eluting MK2 inhibitory peptide to improve hemocompatibility and anti-neointimal activity.Journal of controlled release : official journal of the Controlled Release Society · 2017Article
- Diagnostic value of microRNA-143 in predicting in-stent restenosis for patients with lower extremity arterial occlusive disease.European journal of medical research · 2017Article
- Targeting Mitogen-Activated Protein Kinase-Activated Protein Kinase 2 (MAPKAPK2, MK2): Medicinal Chemistry Efforts To Lead Small Molecule Inhibitors to Clinical Trials.Journal of medicinal chemistry · 2016Review
- Papaverine Prevents Vasospasm by Regulation of Myosin Light Chain Phosphorylation and Actin Polymerization in Human Saphenous Vein.PloS one · 2016Article
- MK2 inhibitory peptide delivered in nanopolyplexes prevents vascular graft intimal hyperplasia.Science translational medicine · 2015Article
- Brilliant blue FCF as an alternative dye for saphenous vein graft marking: effect on conduit function.JAMA surgery · 2014Article
- Targeting methicillin-resistant Staphylococcus aureus with short salt-resistant synthetic peptides.Antimicrobial agents and chemotherapy · 2014Article
- Efficacy of short novel antimicrobial and anti-inflammatory peptides in a mouse model of methicillin-resistant Staphylococcus aureus (MRSA) skin infection.Drug design, development and therapy · 2014Article
- Characterization of endocytic uptake of MK2-inhibitor peptides.Journal of peptide science : an official publication of the European Peptide Society · 2013Article
- Review
- Bladder smooth muscle organ culture preparation maintains the contractile phenotype.American journal of physiology. Renal physiology · 2012Article
- Inhibition of Mitogen Activated Protein Kinase Activated Protein Kinase II with MMI-0100 reduces intimal hyperplasia ex vivo and in vivo.Vascular pharmacologyArticle
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 1 country.
Funding
Abstract
objectiveThe present study was aimed at developing a new cell-permeant peptide inhibitor (MK2i) of the kinase that phosphorylates and activates heat-shock protein (HSP)27 (MAPKAP kinase II), and evaluating the ability of this peptide to inhibit HSP27 phosphorylation and intimal thickening.
methodsThe ability of MK2i to reduce HSP27 phosphorylation and cell migration was evaluated in A7R5 cells stimulated with arsenite or lysophosphatidic acid. Stable isotopic labeling using amino acids in cell culture, in combination with liquid chromatography mass spectrometry, was used to characterize the effect of MK2i on global protein expression in fibroblasts. The effect of MK2i on intimal thickening and connective tissue growth factor expression was evaluated in human saphenous vein (HSV) rings maintained with 30% fetal bovine serum for 14 days by light microscopy and immunoblotting.
resultsPretreatment of cells with MK2i (10 μM) prior to arsenite or lysophosphatidic acid stimulation decreased phosphorylation of HSP27 (36% ± 9% and 33% ± 10%, respectively) compared with control (not pretreated) cells. MK2i also inhibited A7R5 migration, and downregulated the transforming growth factor-induced expression of collagen and fibronectin in keloid cells, two major matrix proteins involved in the development of intimal hyperplasia. Treatment of HSV segments with MK2i enhanced relaxation, reduced HSP27 phosphorylation (40% ± 17%), connective tissue growth factor expression (17% ± 5%), and intimal thickness (48.2% ± 10.5%) compared with untreated segments. On the other hand, treatment with a recombinant fusion protein containing a cell-permeant peptide attached to the HSP27 sequence increased intimal thickness of HSV segments by 48% ± 14%.
conclusionOur results suggest that HSP27 may play a role in the development of processes leading to intimal hyperplasia in HSV, and reduction of HSP27 phosphorylation by MK2i may be a potential strategy to inhibit the development of intimal hyperplasia in HSV to prevent the autologous vascular graft failure.
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