Medical & Biological Engineering & Computing

, Volume 46, Issue 5, pp 469–478

Endothelial cytoskeletal elements are critical for flow-mediated dilation in human coronary arterioles

  • Yanping Liu
  • Hongwei Li
  • Aaron H. Bubolz
  • David X. Zhang
  • David D. Gutterman
Special Issue

DOI: 10.1007/s11517-008-0331-1

Cite this article as:
Liu, Y., Li, H., Bubolz, A.H. et al. Med Biol Eng Comput (2008) 46: 469. doi:10.1007/s11517-008-0331-1

Abstract

Mitochondrial H2O2 contributes to flow-mediated dilation (FMD) in human coronary arterioles (HCA). We examined the hypothesis that the endothelial cytoskeleton plays a critical role in transducing endothelial wall shear stress into a stimulus for releasing mitochondrial ROS. Phallacidin together with α-, β-tubulin antibodies and Mito-Tracker Red showed the proximity of F-actin, microtubules and mitochondria in endothelial cells. Cytochalasin D (CytoD) and nocodazole (Noc) disrupted endothelial F-actin and microtubules in HCA, respectively, concurrent with a reduction in the generation of cytosolic O2•− and H2O2 (hydroethidine and dichlorodihydrofluorescein fluorescence) and mitochondrial superoxide (mitoSox) during flow (control: 3.5 ± 1.6, Cyto D: 0.51 ± 0.2, Noc: 0.81 ± 0.6). FMD, but not the dilation to bradykinin or papaverine, was reduced by Cyto D (26 ± 10% vs. 56 ± 3%) or Noc (26 ± 11% vs. 58 ± 7%). These results suggest that cytoskeletal elements are a critical component of the signaling mechanism linking endothelial shear stress and mitochondrial release of ROS in the human coronary microcirculation.

Keywords

Shear stressCytoskeletonCoronary microcirculationOxidative stress

Copyright information

© International Federation for Medical and Biological Engineering 2008

Authors and Affiliations

  • Yanping Liu
    • 4
  • Hongwei Li
    • 5
  • Aaron H. Bubolz
    • 1
    • 2
    • 3
  • David X. Zhang
    • 1
    • 2
    • 3
  • David D. Gutterman
    • 1
    • 2
    • 3
  1. 1.Department of MedicineMedical College of WisconsinMilwaukeeUSA
  2. 2.The Cardiovascular CenterMilwaukeeUSA
  3. 3.The Medical College of Wisconsin, The Veterans Administration Medical CenterMilwaukeeUSA
  4. 4.The National Center for Research ResourcesNational Institutes of HealthBethesdaUSA
  5. 5.The Heart and Vessel Diseases Center, Beijing Friendship HospitalCapital University of Medical SciencesBeijingPeople’s Republic of China