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Loss of One Copy of...
Loss of One Copy of Zfp148 Reduces Lesional Macrophage Proliferation and Atherosclerosis in Mice by Activating p53
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- Sayin, Volkan I., 1983 (författare)
- Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Institutionen för biomedicin,Wallenberg Laboratory,Institute of Biomedicine
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- Khan, Omar M., 1980 (författare)
- Gothenburg University,Göteborgs universitet,Sahlgrenska Cancer Center
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- Pehlivanoglu, Lara (författare)
- Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Wallenberg Laboratory
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- Staffas, Anna, 1982 (författare)
- Gothenburg University,Göteborgs universitet,Sahlgrenska Cancer Center
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- Ibrahim, Mohamed X (författare)
- Gothenburg University,Göteborgs universitet,Sahlgrenska Cancer Center
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- Asplund, Annika, 1979 (författare)
- Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Wallenberg Laboratory
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- Ågren, Pia (författare)
- Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Wallenberg Laboratory
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- Nilton, Anna (författare)
- Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Wallenberg Laboratory
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- Bergström, Göran, 1964 (författare)
- Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Wallenberg Laboratory
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- Bergö, Martin, 1970 (författare)
- Gothenburg University,Göteborgs universitet,Sahlgrenska Cancer Center
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- Borén, Jan, 1963 (författare)
- Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Wallenberg Laboratory
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- Lindahl, Per, 1967 (författare)
- Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Institutionen för biomedicin,Wallenberg Laboratory,Institute of Biomedicine
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(creator_code:org_t)
- Ovid Technologies (Wolters Kluwer Health), 2014
- 2014
- Engelska.
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Ingår i: Circulation Research. - : Ovid Technologies (Wolters Kluwer Health). - 0009-7330 .- 1524-4571. ; 115:9, s. 781-791
- Relaterad länk:
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Rationale: Cell proliferation and cell cycle control mechanisms are thought to play central roles in the pathogenesis of atherosclerosis. The transcription factor Zinc finger protein 148 (Zfp148) was shown recently to maintain cell proliferation under oxidative conditions by suppressing p53, a checkpoint protein that arrests proliferation in response to various stressors. It is established that inactivation of p53 accelerates atherosclerosis, but whether increased p53 activation confers protection against the disease remains to be determined. Objective: We aimed to test the hypothesis that Zfp148 deficiency reduces atherosclerosis by unleashing p53 activity. Methods and Results: Mice harboring a gene-trap mutation in the Zfp148 locus (Zfp148(gt/+)) were bred onto the apolipoprotein E (Apoe)(-/-) genetic background and fed a high-fat or chow diet. Loss of 1 copy of Zfp148 markedly reduced atherosclerosis without affecting lipid metabolism. Bone marrow transplantation experiments revealed that the effector cell is of hematopoietic origin. Peritoneal macrophages and atherosclerotic lesions from Zfp148(gt/+)Apoe(-/-) mice showed increased levels of phosphorylated p53 compared with controls, and atherosclerotic lesions contained fewer proliferating macrophages. Zfp148(gt/+) Apoe(-/-) mice were further crossed with p53-null mice (Trp53(-/-) [the gene encoding p53]). There was no difference in atherosclerosis between Zfp148(gt/+) Apoe(-/-) mice and controls on a Trp53(+/-) genetic background, and there was no difference in levels of phosphorylated p53 or cell proliferation. Conclusions: Zfp148 deficiency increases p53 activity and protects against atherosclerosis by causing proliferation arrest of lesional macrophages, suggesting that drugs targeting macrophage proliferation may be useful in the treatment of atherosclerosis.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Kardiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cardiac and Cardiovascular Systems (hsv//eng)
Nyckelord
- atherosclerosis
- cell proliferation
- genes
- p53
- macrophages
- mice
- transgenic
- Zfp148 protein
- mouse
- TRANSCRIPTION FACTOR ZBP-89
- GENE-EXPRESSION
- LOCAL PROLIFERATION
- CELL-PROLIFERATION
- DEFICIENCY LEADS
- KNOCKOUT MICE
- IN-VIVO
- APOPTOSIS
- INFLAMMATION
- RECRUITMENT
- Cardiac & Cardiovascular Systems
- Hematology
- Peripheral Vascular
- Disease
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Sayin, Volkan I. ...
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Khan, Omar M., 1 ...
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Pehlivanoglu, La ...
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Staffas, Anna, 1 ...
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Ibrahim, Mohamed ...
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Asplund, Annika, ...
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Ågren, Pia
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Nilton, Anna
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Bergström, Göran ...
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Bergö, Martin, 1 ...
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Borén, Jan, 1963
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Lindahl, Per, 19 ...
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Göteborgs universitet