Albumin-based microbubbles bind up-regulated scavenger receptors following vascular injury

Daniel R Anderson, Michael J. Duryee, Rajeev K. Anchan, Robert P. Garvin, Michael D. Johnston, Thomas Richard Porter, Geoffrey Milton Thiele, Lynell Warren Klassen

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

We have shown previously that perfluorocarbon-exposed sonicated dextrose albumin (PESDA) microbubbles bind to injured vascular tissue and can be detected with ultrasound imaging techniques. Prior studies have shown that scavenger receptors (SRs) are regulators of innate and adaptive immune responses and are involved in the progression of vascular disease such as atherosclerosis. In this study, we sought to determine the molecular mechanism of PESDA binding to ballooninjured vasculature. RT-PCR analysis of angioplastied aortas demonstrated a significantly (p ≤ 0.01) increased expression of SRs. Binding to SRs was confirmed using SR-expressing CHO cells, and this binding was blocked by competitive inhibition with the SR-binding ligands oxidized LDL and malondialdehyde-acetaldehyde-modified LDL. Confocal imaging confirmed the co-localization of PESDA microbubbles to CD36, SRB-1, and Toll-like receptor 4, but not to monocytes/macrophages. This study demonstrates that PESDA binds to SRs and that this binding is in major part dependent upon the oxidized nature of PESDA microbubble shell proteins. The extent of SR mRNA expression was increased with injury and associated with microbubble retention as defined by scanning electron microscopy and immunohistochemistry. These findings clarify the mechanisms of how albumin-based microbubbles bind to injured and inflamed vasculature and further support the potential of this imaging technique to detect early vascular innate inflammatory pathophysiologic processes.

Original languageEnglish (US)
Pages (from-to)40645-40653
Number of pages9
JournalJournal of Biological Chemistry
Volume285
Issue number52
DOIs
StatePublished - Dec 24 2010

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Scavenger Receptors
Microbubbles
Vascular System Injuries
Fluorocarbons
Albumins
Glucose
Imaging techniques
Blood Vessels
Toll-Like Receptor 4
Acetaldehyde
CHO Cells
Macrophages
Adaptive Immunity
Malondialdehyde
Vascular Diseases
Innate Immunity
Electron Scanning Microscopy
Aorta
Monocytes
Ultrasonography

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Albumin-based microbubbles bind up-regulated scavenger receptors following vascular injury. / Anderson, Daniel R; Duryee, Michael J.; Anchan, Rajeev K.; Garvin, Robert P.; Johnston, Michael D.; Porter, Thomas Richard; Thiele, Geoffrey Milton; Klassen, Lynell Warren.

In: Journal of Biological Chemistry, Vol. 285, No. 52, 24.12.2010, p. 40645-40653.

Research output: Contribution to journalArticle

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