The epigenetic factor PCAF regulates vascular inflammation and is essential for intimal hyperplasia development
| Autor: | H.A.B. Peters, Fabiana Baghana, J. Wouter Jukema, M.M. Ewing, Peter J. van den Elsen, Paul H.A. Quax, A.J.N.M. Bastiaansen, Céline Gongora, Rob C. M. de Jong, J.C. Karper, Margreet R. de Vries |
|---|---|
| Přispěvatelé: | Pathology, Amsterdam Neuroscience - Neuroinfection & -inflammation, Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Interuniversity Cardiology Institute Netherlands |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
Male
Vascular smooth muscle Pathology and Laboratory Medicine Biochemistry Mice 0302 clinical medicine Animal Cells Small interfering RNAs lcsh:Science Immune Response ComputingMilieux_MISCELLANEOUS Innate Immune System NF-kappa B Arteries Tunica intima 3. Good health Femoral Artery Nucleic acids Blood PCAF Cytokines Cellular Types Vasculitis medicine.medical_specialty Immune Cells Primary Cell Culture Immunology CCL2 03 medical and health sciences Apolipoproteins E Signs and Symptoms medicine.artery Genetics Humans Non-coding RNA [SDV.GEN]Life Sciences [q-bio]/Genetics Blood Cells Tumor Necrosis Factor-alpha Macrophages lcsh:R Biology and Life Sciences Molecular Development medicine.disease 030104 developmental biology Endocrinology Blood Vessels lcsh:Q Gene expression Developmental Biology 0301 basic medicine Intimal hyperplasia Physiology [SDV]Life Sciences [q-bio] lcsh:Medicine Femoral artery 030204 cardiovascular system & hematology Epigenesis Genetic White Blood Cells Immune Physiology Leukocytes Medicine and Health Sciences p300-CBP Transcription Factors Chemokine CCL2 Mice Knockout Multidisciplinary Animal Models Body Fluids medicine.anatomical_structure Experimental Organism Systems medicine.symptom Anatomy Signal Transduction Research Article Myocytes Smooth Muscle Inflammation Mouse Models Research and Analysis Methods Model Organisms Downregulation and upregulation Diagnostic Medicine Internal medicine medicine Cell Adhesion Animals Hyperplasia business.industry Interleukin-6 Terpenes Cell Biology Femoral Arteries Gene regulation Disease Models Animal [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics Immune System Cancer research Cardiovascular Anatomy RNA business Tunica Intima |
| Zdroj: | PLoS ONE, Vol 12, Iss 10, p e0185820 (2017) PLOS ONE PLoS ONE, 12(10) PLoS ONE, 12(10):e0185820. Public Library of Science PLoS ONE PLoS ONE, Public Library of Science, 2017, 12 (10), pp.e0185820. ⟨10.1371/journal.pone.0185820⟩ De Jong, R C M, Ewing, M M, De Vries, M R, Karper, J C, Bastiaansen, A J N M, Peters, H A B, Baghana, F, Van Den Elsen, P J, Gongora, C, Jukema, J W & Quax, P H A 2017, ' The epigenetic factor PCAF regulates vascular inflammation and is essential for intimal hyperplasia development ', PLoS ONE, vol. 12, no. 10, e0185820 . https://doi.org/10.1371/journal.pone.0185820 |
| ISSN: | 1932-6203 |
| Popis: | Objective Genetic P300/CBP-associated factor (PCAF) variation affects restenosis-risk in patients. PCAF has lysine acetyltransferase activity and promotes nuclear factor kappa-beta (NFκB)-mediated inflammation, which drives post-interventional intimal hyperplasia development. We studied the contributing role of PCAF in post-interventional intimal hyperplasia. Methods and results PCAF contribution to inflammation and intimal hyperplasia was assessed in leukocytes, macrophages and vascular smooth muscle cells (vSMCs) in vitro and in a mouse model for intimal hyperplasia, in which a cuff is placed around the femoral artery. PCAF deficiency downregulate CCL2, IL-6 and TNF-alpha expression, as demonstrated on cultured vSMCs, leukocytes and macrophages. PCAF KO mice showed a 71.8% reduction of vSMC-rich intimal hyperplasia, a 73.4% reduction of intima/media ratio and a 63.7% reduction of luminal stenosis after femoral artery cuff placement compared to wild type (WT) mice. The association of PCAF and vascular inflammation was further investigated using the potent natural PCAF inhibitor garcinol. Garcinol treatment reduced CCL2 and TNF-alpha expression, as demonstrated on cultured vSMCs and leukocytes. To assess the effect of garcinol treatment on vascular inflammation we used hypercholesterolemic ApoE*3-Leiden mice. After cuff placement, garcinol treatment resulted in reduced arterial leukocyte and macrophage adherence and infiltration after three days compared to untreated animals. Conclusions These results identify a vital role for the lysine acetyltransferase PCAF in the regulation of local inflammation after arterial injury and likely the subsequent vSMC proliferation, responsible for intimal hyperplasia. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|