Shear modulates adhesion of ultrasound contrast microbubbles targeted to dysfunctional endothelium

Gregory E. Weller, F. S. Villanueva, A. L. Klibanov, W. R. Wagner

Research output: Contribution to journalConference article

1 Citation (Scopus)

Abstract

Endothelial dysfunction, as occurs in pre-clinical atherosclerosis and organ transplant rejection, is characterized by increased endothelial cell (EC) surface expression of inflammatory markers including intercellular adhesion molecule-1 (ICAM). Previously, we have shown that lipid-based ultrasound contrast microbubbles (MBs) selectively adhere to inflamed ECs when conjugated to anti-ICAM monoclonal antibodies (Ab). Here, we hypothesized that the adhesion of targeted MBs to ECs from flow is shear-rate dependent. Microbubbles were conjugated via avidin/biotin bridging chemistry to anti-ICAM mAb (60,000 Ab/MB surface density). In a parallel plate chamber, MBs were perfused across coverslips of normal or interleukin-1β-activated cultured human coronary artery ECs at selected wall shear rates for 3 min and washed. Adhesion to ECs was quantified in 20 random microscopic fields per coverslip (mean MBs/cell±SD). Adhesion decreased with increasing shear rate to both normal (100s-1=0.84±1.7, 175s-1=0.58±0.40, 250s-1=0.40±0.45, 350s-1=0.16±0.14, 500s-1=0.04±0.02) and activated ECs (100s-1=3.0±2.7, 175s-1=2.6±0.77, 250s-1=2.1±1.3, 350s-1=1.2±0.90, 500s-1=0.49±0.09). Adherence was greater to activated than normal ECs (p<0.001), and decreased with increasing shear rate (p=0.02). These data demonstrate that adhesion of targeted MBs to ECs is highly dependent upon the local shear environment. This relationship has important implications for the design of targeted contrast agents for ultrasonic assessment of endothelial dysfunction.

Original languageEnglish (US)
Pages (from-to)899-900
Number of pages2
JournalAnnual International Conference of the IEEE Engineering in Medicine and Biology - Proceedings
Volume2
StatePublished - Dec 1 2002
EventProceedings of the 2002 IEEE Engineering in Medicine and Biology 24th Annual Conference and the 2002 Fall Meeting of the Biomedical Engineering Society (BMES / EMBS) - Houston, TX, United States
Duration: Oct 23 2002Oct 26 2002

Fingerprint

Microbubbles
Endothelium
Adhesion
Ultrasonics
Shear deformation
Intercellular Adhesion Molecule-1
Molecules
Transplants
Monoclonal antibodies
Avidin
Endothelial cells
Graft Rejection
Biotin
Interleukin-1
Antibodies
Lipids
Contrast Media
Atherosclerosis
Coronary Vessels
Endothelial Cells

All Science Journal Classification (ASJC) codes

  • Signal Processing
  • Biomedical Engineering
  • Computer Vision and Pattern Recognition
  • Health Informatics

Cite this

@article{dae00c45066f41f7be1ceaa5770020cd,
title = "Shear modulates adhesion of ultrasound contrast microbubbles targeted to dysfunctional endothelium",
abstract = "Endothelial dysfunction, as occurs in pre-clinical atherosclerosis and organ transplant rejection, is characterized by increased endothelial cell (EC) surface expression of inflammatory markers including intercellular adhesion molecule-1 (ICAM). Previously, we have shown that lipid-based ultrasound contrast microbubbles (MBs) selectively adhere to inflamed ECs when conjugated to anti-ICAM monoclonal antibodies (Ab). Here, we hypothesized that the adhesion of targeted MBs to ECs from flow is shear-rate dependent. Microbubbles were conjugated via avidin/biotin bridging chemistry to anti-ICAM mAb (60,000 Ab/MB surface density). In a parallel plate chamber, MBs were perfused across coverslips of normal or interleukin-1β-activated cultured human coronary artery ECs at selected wall shear rates for 3 min and washed. Adhesion to ECs was quantified in 20 random microscopic fields per coverslip (mean MBs/cell±SD). Adhesion decreased with increasing shear rate to both normal (100s-1=0.84±1.7, 175s-1=0.58±0.40, 250s-1=0.40±0.45, 350s-1=0.16±0.14, 500s-1=0.04±0.02) and activated ECs (100s-1=3.0±2.7, 175s-1=2.6±0.77, 250s-1=2.1±1.3, 350s-1=1.2±0.90, 500s-1=0.49±0.09). Adherence was greater to activated than normal ECs (p<0.001), and decreased with increasing shear rate (p=0.02). These data demonstrate that adhesion of targeted MBs to ECs is highly dependent upon the local shear environment. This relationship has important implications for the design of targeted contrast agents for ultrasonic assessment of endothelial dysfunction.",
author = "Weller, {Gregory E.} and Villanueva, {F. S.} and Klibanov, {A. L.} and Wagner, {W. R.}",
year = "2002",
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Shear modulates adhesion of ultrasound contrast microbubbles targeted to dysfunctional endothelium. / Weller, Gregory E.; Villanueva, F. S.; Klibanov, A. L.; Wagner, W. R.

In: Annual International Conference of the IEEE Engineering in Medicine and Biology - Proceedings, Vol. 2, 01.12.2002, p. 899-900.

Research output: Contribution to journalConference article

TY - JOUR

T1 - Shear modulates adhesion of ultrasound contrast microbubbles targeted to dysfunctional endothelium

AU - Weller, Gregory E.

AU - Villanueva, F. S.

AU - Klibanov, A. L.

AU - Wagner, W. R.

PY - 2002/12/1

Y1 - 2002/12/1

N2 - Endothelial dysfunction, as occurs in pre-clinical atherosclerosis and organ transplant rejection, is characterized by increased endothelial cell (EC) surface expression of inflammatory markers including intercellular adhesion molecule-1 (ICAM). Previously, we have shown that lipid-based ultrasound contrast microbubbles (MBs) selectively adhere to inflamed ECs when conjugated to anti-ICAM monoclonal antibodies (Ab). Here, we hypothesized that the adhesion of targeted MBs to ECs from flow is shear-rate dependent. Microbubbles were conjugated via avidin/biotin bridging chemistry to anti-ICAM mAb (60,000 Ab/MB surface density). In a parallel plate chamber, MBs were perfused across coverslips of normal or interleukin-1β-activated cultured human coronary artery ECs at selected wall shear rates for 3 min and washed. Adhesion to ECs was quantified in 20 random microscopic fields per coverslip (mean MBs/cell±SD). Adhesion decreased with increasing shear rate to both normal (100s-1=0.84±1.7, 175s-1=0.58±0.40, 250s-1=0.40±0.45, 350s-1=0.16±0.14, 500s-1=0.04±0.02) and activated ECs (100s-1=3.0±2.7, 175s-1=2.6±0.77, 250s-1=2.1±1.3, 350s-1=1.2±0.90, 500s-1=0.49±0.09). Adherence was greater to activated than normal ECs (p<0.001), and decreased with increasing shear rate (p=0.02). These data demonstrate that adhesion of targeted MBs to ECs is highly dependent upon the local shear environment. This relationship has important implications for the design of targeted contrast agents for ultrasonic assessment of endothelial dysfunction.

AB - Endothelial dysfunction, as occurs in pre-clinical atherosclerosis and organ transplant rejection, is characterized by increased endothelial cell (EC) surface expression of inflammatory markers including intercellular adhesion molecule-1 (ICAM). Previously, we have shown that lipid-based ultrasound contrast microbubbles (MBs) selectively adhere to inflamed ECs when conjugated to anti-ICAM monoclonal antibodies (Ab). Here, we hypothesized that the adhesion of targeted MBs to ECs from flow is shear-rate dependent. Microbubbles were conjugated via avidin/biotin bridging chemistry to anti-ICAM mAb (60,000 Ab/MB surface density). In a parallel plate chamber, MBs were perfused across coverslips of normal or interleukin-1β-activated cultured human coronary artery ECs at selected wall shear rates for 3 min and washed. Adhesion to ECs was quantified in 20 random microscopic fields per coverslip (mean MBs/cell±SD). Adhesion decreased with increasing shear rate to both normal (100s-1=0.84±1.7, 175s-1=0.58±0.40, 250s-1=0.40±0.45, 350s-1=0.16±0.14, 500s-1=0.04±0.02) and activated ECs (100s-1=3.0±2.7, 175s-1=2.6±0.77, 250s-1=2.1±1.3, 350s-1=1.2±0.90, 500s-1=0.49±0.09). Adherence was greater to activated than normal ECs (p<0.001), and decreased with increasing shear rate (p=0.02). These data demonstrate that adhesion of targeted MBs to ECs is highly dependent upon the local shear environment. This relationship has important implications for the design of targeted contrast agents for ultrasonic assessment of endothelial dysfunction.

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