Regulation and splicing of scavenger receptor class B type I in human macrophages and atherosclerotic plaques
Artikel i vetenskaplig tidskrift, 2005

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.

Macrophages/drug effects/*metabolism


Amino Acid Motifs

Lysosome-Associated Membrane Glycoproteins/chemistry/genetics/metabolism

Alternative Splicing


Amino Acid Sequence



Class B/chemistry/genetics/*metabolism



Cell Hypoxia

Base Sequence

Protein Isoforms


Scavenger Receptors

Gene Expression Regulation/drug effects


src Homology Domains


Molecular Sequence Data





Per Anders Svensson

Göteborgs universitet

Mikael Englund

Göteborgs universitet

Magnus S C Snäckestrand

Göteborgs universitet

Daniel Hägg

Göteborgs universitet

Bertil Ohlsson

Göteborgs universitet

V. Stemme

Lillemor Mattsson Hultén

Göteborgs universitet

Dag Thelle

Göteborgs universitet

Björn Fagerberg

Göteborgs universitet

Olov Wiklund

Göteborgs universitet

Lena M S Carlsson

Göteborgs universitet

Björn Carlsson

Göteborgs universitet

BMC Cardiovascular Disorders

1471-2261 (ISSN)

Vol. 5 25-





Mer information