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Updated: Aug 16, 2026

A Human Ex Vivo Atherosclerotic Plaque Model to Study Lesion Biology
Published on: May 6, 2014
Regulation and splicing of scavenger receptor class B type I in human macrophages and atherosclerotic plaques
Per-Arne Svensson1, Mikael C O Englund, Magnus S C Snäckestrand
1Research Centre for Endocrinology & Metabolism, Department of Internal Medicine, The Sahlgrenska Academy, Göteborg University, S-413 45 Göteborg, Sweden. Per-Arne.Svensson@medic.gu.se
Insights
Scavenger receptor class B type I (SR-BI) expression in human macrophages is influenced by proatherogenic factors but does not differ between atherosclerosis patients and healthy individuals. A novel SR-BI isoform, SR-BIII, was identified in human macrophages and plaques.
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- Atherosclerosis Research
Background:
- High-density lipoprotein (HDL) plays a protective role in cardiovascular health via reverse cholesterol transport.
- Scavenger receptor class B type I (SR-BI) facilitates cholesterol uptake to HDL, but its role in human atherosclerosis is not fully understood.
- Investigating SR-BI expression in human macrophages and atherosclerotic plaques is crucial for understanding its involvement in human cardiovascular disease.
Purpose of the Study:
- To investigate the expression of SR-BI and its isoforms in human macrophages and atherosclerotic plaques.
- To determine the effect of proatherogenic stimuli like hypoxia and minimally modified low-density lipoprotein (mmLDL) on SR-BI expression in human macrophages.
- To compare SR-BI expression levels in macrophages from patients with atherosclerosis versus healthy controls.
Main Methods:
- Human monocyte-derived macrophages from healthy subjects were treated with hypoxia and mmLDL.
- SR-BI expression was quantified using real-time PCR.
- SR-BI isoforms were identified and characterized in macrophages and atherosclerotic plaques using RT-PCR and DNA sequencing.
Main Results:
- Hypoxia decreased SR-BI expression, while mmLDL increased it in human macrophages.
- No significant difference in SR-BI expression was observed between macrophages from atherosclerosis patients and healthy controls.
- Three SR-BI isoforms (SR-BI, SR-BII, and a novel SR-BIII) were detected in human macrophages and atherosclerotic plaques, with SR-BIII possessing a unique C-terminal domain.
Conclusions:
- SR-BI expression in human macrophages is modulated by proatherogenic stimuli but does not appear to be a common cause of atherosclerosis.
- Altered SR-BI expression is unlikely to be a primary driver of atherosclerosis in humans.
- A novel SR-BI isoform, SR-BIII, has been identified and characterized in human macrophages and atherosclerotic lesions.
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.
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