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Regulation and spli...
Regulation and splicing of scavenger receptor class B type I in human macrophages and atherosclerotic plaques
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- Svensson, Per-Arne, 1969 (author)
- Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Institutionen för invärtesmedicin, Avdelningen för kroppssammansättning och metabolism,Wallenberg Laboratory,Institute of Internal Medicine, Dept of Body Composition and Metabolism
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- Englund, Mikael C. O., 1971 (author)
- Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Wallenberg Laboratory,University of Gothenburg
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- Carlsson, Lena M S, 1957 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för invärtesmedicin, Avdelningen för kroppssammansättning och metabolism,Institute of Internal Medicine, Dept of Body Composition and Metabolism,University of Gothenburg
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- Hägg, Daniel, 1974 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för invärtesmedicin, Avdelningen för kroppssammansättning och metabolism,Institute of Internal Medicine, Dept of Body Composition and Metabolism,University of Gothenburg
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- Ohlsson, Bertil, 1954 (author)
- Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Wallenberg Laboratory,University of Gothenburg
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Stemme, V. (author)
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- Mattsson Hultén, Lillemor, 1951 (author)
- Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Wallenberg Laboratory,University of Gothenburg
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- Thelle, Dag, 1942 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för invärtesmedicin, Avdelningen för internmedicin,Institute of Internal Medicine, Dept of Medicine,University of Gothenburg
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- Fagerberg, Björn, 1943 (author)
- Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Wallenberg Laboratory,University of Gothenburg
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- Wiklund, Olov, 1943 (author)
- Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Wallenberg Laboratory,University of Gothenburg
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- Carlsson, Lena M S, 1957 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för invärtesmedicin, Avdelningen för kroppssammansättning och metabolism,Institute of Internal Medicine, Dept of Body Composition and Metabolism
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- Carlsson, Björn, 1958 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för invärtesmedicin, Avdelningen för kroppssammansättning och metabolism,Institute of Internal Medicine, Dept of Body Composition and Metabolism,University of Gothenburg
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- Svensson, Per Anders, 1959 (author)
- Göteborgs universitet,University of Gothenburg
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(creator_code:org_t)
- 2005-08-25
- 2005
- English.
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In: BMC Cardiovasc Disord. - : Springer Science and Business Media LLC. - 1471-2261. ; 5
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Abstract
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- BACKGROUND: The protective role of high-density lipoprotein (HDL) in the cardiovascular system is related to its role in the reverse transport of cholesterol from the arterial wall to the liver for subsequent excretion via the bile. Scavenger receptor class B type I (SR-BI) binds HDL and mediates selective uptake of cholesterol ester and cellular efflux of cholesterol to HDL. The role of SR-BI in atherosclerosis has been well established in murine models but it remains unclear whether SR-BI plays an equally important role in atherosclerosis in humans. The aim of this study was to investigate the expression of SR-BI and its isoforms in human macrophages and atherosclerotic plaques. METHODS: The effect of hypoxia and minimally modified low-density lipoprotein (mmLDL), two proatherogenic stimuli, on SR-BI expression was studied in human monocyte-derived macrophages from healthy subjects using real-time PCR. In addition, SR-BI expression was determined in macrophages obtained from subjects with atherosclerosis (n = 15) and healthy controls (n = 15). Expression of SR-BI isoforms was characterized in human atherosclerotic plaques and macrophages using RT-PCR and DNA sequencing. RESULTS: SR-BI expression was decreased in macrophages after hypoxia (p < 0.005). In contrast, SR-BI expression was increased by exposure to mmLDL (p < 0.05). There was no difference in SR-BI expression in macrophages from patients with atherosclerosis compared to controls. In both groups, SR-BI expression was increased by exposure to mmLDL (p < 0.05). Transcripts corresponding to SR-BI and SR-BII were detected in macrophages. In addition, a third isoform, referred to as SR-BIII, was discovered. All three isoforms were also expressed in human atherosclerotic plaque. Compared to the other isoforms, the novel SR-BIII isoform was predicted to have a unique intracellular C-terminal domain containing 53 amino acids. CONCLUSION: We conclude that SR-BI is regulated by proatherogenic stimuli in humans. However, we found no differences between subjects with atherosclerosis and healthy controls. This indicates that altered SR-BI expression is not a common cause of atherosclerosis. In addition, we identified SR-BIII as a novel isoform expressed in human macrophages and in human atherosclerotic plaques.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine (hsv//eng)
Keyword
- Adult
- Alternative Splicing
- Amino Acid Motifs
- Amino Acid Sequence
- Atherosclerosis/etiology/metabolism
- Base Sequence
- Cell Hypoxia
- Cells
- Cultured
- Female
- Gene Expression Regulation/drug effects
- Humans
- Lipoproteins
- LDL/pharmacology
- Lysosome-Associated Membrane Glycoproteins/chemistry/genetics/metabolism
- Macrophages/drug effects/*metabolism
- Male
- Molecular Sequence Data
- Protein Isoforms
- RNA
- Messenger/metabolism
- Scavenger Receptors
- Class B/chemistry/genetics/*metabolism
- Sialoglycoproteins/chemistry/genetics/metabolism
- src Homology Domains
- Macrophages/drug effects/*metabolism
Publication and Content Type
- ref (subject category)
- art (subject category)
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Svensson, Per-Ar ...
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Englund, Mikael ...
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Carlsson, Lena M ...
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Hägg, Daniel, 19 ...
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Ohlsson, Bertil, ...
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Stemme, V.
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Mattsson Hultén, ...
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Thelle, Dag, 194 ...
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Fagerberg, Björn ...
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Wiklund, Olov, 1 ...
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Carlsson, Björn, ...
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Svensson, Per An ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
- Articles in the publication
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BMC Cardiovasc D ...
- By the university
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University of Gothenburg
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Chalmers University of Technology