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A CYP26B1 polymorph...
A CYP26B1 polymorphism enhances retinoic acid catabolism and may aggravate atherosclerosis
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- Krivospitskaya, Olesya, 1983- (author)
- Örebro universitet,Hälsoakademin,Department of Clinical Medicine
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- Elmabsout, Ali Ateia, 1977- (author)
- Örebro universitet,Institutionen för hälsovetenskap och medicin,Department of Clinical Medicine
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- Sundman, Eva (author)
- Karolinska Institutet
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- Söderström, Leif A. (author)
- Karolinska Institutet
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- Ovchinnikova, Olga (author)
- Karolinska Institutet
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- Gidlöf, Andreas C. (author)
- Department of Anesthesiology, Surgical Services and Intensive Care Medicine, Karolinska University Hospital Solna, Stockholm, Sweden; Karolinska Institutet, Stockholm, Sweden
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- Scherbak, Nikolai, 1967- (author)
- Örebro universitet,Institutionen för naturvetenskap och teknik
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- Norata, Giuseppe Danilo (author)
- Atherosclerosis Research Unit, Center for Molecular Medicine, Department of Medicine, Karolinska Institutet, Stockholm, Sweden; Department of Pharmacological Sciences University of Milan, Milan, Italy
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- Samnegård, Ann (author)
- Karolinska Institutet
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- Törmä, Hans (author)
- Uppsala universitet,Dermatologi och venereologi
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- Abdel-Halim, Samy M., 1961- (author)
- Division of Respiratory Medicine and Allergology, Department of Clinical Sciences, Danderyd Hospital, Stockholm, Sweden; Karolinska Institutet, Stockholm, Sweden
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- Jansson, Jan-Håkan (author)
- Umeå universitet,Medicin
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- Eriksson, Per (author)
- Karolinska Institutet
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- Sirsjö, Allan, 1959- (author)
- Örebro universitet,Institutionen för hälsovetenskap och medicin,Department of Clinical Medicine
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- Olofsson, Peder S. (author)
- Karolinska Institutet
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(creator_code:org_t)
- 2012-03-09
- 2012
- English.
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In: Molecular Medicine. - New York, USA : The Feinstein Institute for Medical Research. - 1076-1551 .- 1528-3658. ; 18:1, s. 712-718
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Abstract
Subject headings
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- All-trans retinoic acid, controlled by CYP26 enzymes, potentially has beneficial effects in atherosclerosis treatment. This study investigates CYP26B1 in atherosclerosis and effects of a genetic polymorphism in CYP26B1 on retinoid catabolism. We found that CYP26B1 mRNA was induced by retinoic acid in human atherosclerotic arteries and CYP26B1 and the macrophage marker CD68 co-localized in human atherosclerotic lesions. In mice, Cyp26B1 mRNA was higher in atherosclerotic than normal arteries. Databases were queried for non-synonymous CYP26B1 SNPs and rs2241057 selected for further studies. Constructs of the CYP26B1 variants were created and used for production of purified proteins and transfection of macrophage-like cells. The minor variant catabolized retinoic acid with significantly higher efficiency, indicating that rs2241057 is functional and suggesting reduced retinoid availability in tissues with the minor variant. rs2241057 was investigated in a Stockholm Coronary Atherosclerosis Risk Factor (SCARF) subgroup. The minor allele was associated with slightly larger lesions as determined by angiography. In summary, this study identifies the first CYP26B1 polymorphism that alters CYP26B1 capacity to metabolize retinoic acid. CYP26B1 was expressed in macrophage-rich areas of human atherosclerotic lesions, induced by retinoic acid and increased in murine atherosclerosis. Taken together, the results indicate that CYP26B1 capacity is genetically regulated and suggest that local CYP26B1 activity may influence atherosclerosis.
Subject headings
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)
Keyword
- Medicine
- Medicin
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Krivospitskaya, ...
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Elmabsout, Ali A ...
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Sundman, Eva
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Söderström, Leif ...
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Ovchinnikova, Ol ...
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Gidlöf, Andreas ...
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show more...
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Scherbak, Nikola ...
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Norata, Giuseppe ...
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Samnegård, Ann
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Törmä, Hans
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Abdel-Halim, Sam ...
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Jansson, Jan-Håk ...
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Eriksson, Per
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Sirsjö, Allan, 1 ...
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Olofsson, Peder ...
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- About the subject
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Biochemistry and ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Medical Biotechn ...
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and Medical Biotechn ...
- Articles in the publication
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Molecular Medici ...
- By the university
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Örebro University
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Karolinska Institutet
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Uppsala University
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Umeå University