Albumin-based microbubbles bind up-regulated scavenger receptors following vascular injury.
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 balloon-injured 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.
Division of Cardiology, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska 68198-6350, USA. danderso@unmc.edu
Daniel R
DR
Anderson
Michael J
MJ
Duryee
Rajeev K
RK
Anchan
Robert P
RP
Garvin
Michael D
MD
Johnston
Thomas R
TR
Porter
Geoffrey M
GM
Thiele
Lynell W
LW
Klassen
D000818:Animals; D001011:Aorta / Q000293:injuries / Q000378:metabolism / Q000648:ultrastructure; D016466:CHO Cells; D002417:Cattle; D003287:Contrast Media / Q000494:pharmacology*; D006224:Cricetinae; D003412:Cricetulus; D005466:Fluorocarbons / Q000494:pharmacology*; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D008297:Male; D045423:Microbubbles; D051381:Rats; D017207:Rats, Sprague-Dawley; D051116:Receptors, Scavenger / Q000096:biosynthesis*; D012709:Serum Albumin / Q000494:pharmacology*; D000075462:Serum Albumin, Human; D015854:Up-Regulation / Q000187:drug effects*
D003287:Contrast Media; D005466:Fluorocarbons; D051116:Receptors, Scavenger; D012709:Serum Albumin; C094311:dextrose albumin solution; D005947:Glucose; D000075462:Serum Albumin, Human