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.
Abstract

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