Lysine Acetyltransferase PCAF Is a Key Regulator of Arteriogenesis
| Autor: | J. Wouter Jukema, M.M. Ewing, Erna Peters, Tineke C. T. M. van der Pouw Kraan, A.J.N.M. Bastiaansen, Jaap F. Hamming, Hetty C. de Boer, Sabine M.J. Welten, Margreet R. de Vries, Scott M. Moore, A. Yaël Nossent, Ramon Arens, James E. Faber, Paul H.A. Quax |
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| Přispěvatelé: | Molecular cell biology and Immunology, ICaR - Ischemia and repair |
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
T-Lymphocytes
Regulator Neovascularization Physiologic Inflammation P300-CBP Transcription Factors Biology Article Proinflammatory cytokine Histones Mice Ischemia peripheral arterial disease medicine Animals p300-CBP Transcription Factors Enzyme Inhibitors Cells Cultured Mice Knockout Regulation of gene expression Arteritis Terpenes Acetylation Hindlimb Disease Models Animal Histone Gene Expression Regulation PCAF inflammation biology.protein Cancer research p300-CBP-associated factor Arteriogenesis medicine.symptom Transcriptome Cardiology and Cardiovascular Medicine monocytes |
| Zdroj: | Arteriosclerosis, Thrombosis, and Vascular Biology, 33(8), 1902-1910 Arteriosclerosis, Thrombosis, and Vascular Biology, 33(8), 1902-1910. Lippincott Williams and Wilkins Bastiaansen, A J N M, Ewing, M M, de Boer, HC, van der Pouw Kraan, C T M, de Vries, M R, Peters, E A B, Welten, S M J, Arens, R, Moore, S M, Faber, J E, Jukema, J W, Hamming, J F, Nossent, A Y & Quax, P H A 2013, ' Lysine Acetyltransferase PCAF Is a Key Regulator of Arteriogenesis ', Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 33, no. 8, pp. 1902-1910 . https://doi.org/10.1161/ATVBAHA.113.301579 |
| ISSN: | 1079-5642 |
| DOI: | 10.1161/ATVBAHA.113.301579 |
| Popis: | Objective— Therapeutic arteriogenesis, that is, expansive remodeling of preexisting collaterals, using single-action factor therapies has not been as successful as anticipated. Modulation of factors that act as a master switch for relevant gene programs may prove more effective. Transcriptional coactivator p300-CBP–associated factor (PCAF) has histone acetylating activity and promotes transcription of multiple inflammatory genes. Because arteriogenesis is an inflammation-driven process, we hypothesized that PCAF acts as multifactorial regulator of arteriogenesis. Approach and Results— After induction of hindlimb ischemia, blood flow recovery was impaired in both PCAF −/− mice and healthy wild-type mice treated with the pharmacological PCAF inhibitor Garcinol, demonstrating an important role for PCAF in arteriogenesis. PCAF deficiency reduced the in vitro inflammatory response in leukocytes and vascular cells involved in arteriogenesis. In vivo gene expression profiling revealed that PCAF deficiency results in differential expression of 3505 genes during arteriogenesis and, more specifically, in impaired induction of multiple proinflammatory genes. Additionally, recruitment from the bone marrow of inflammatory cells, in particular proinflammatory Ly6C hi monocytes, was severely impaired in PCAF −/− mice. Conclusions— These findings indicate that PCAF acts as master switch in the inflammatory processes required for effective arteriogenesis. |
| Databáze: | OpenAIRE |
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