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Endothelial cytoskeletal elements are critical for flow-mediated dilation in human coronary arterioles. Med Biol Eng Comput 2008 May;46(5):469-78

Date

03/15/2008

Pubmed ID

18340474

Pubmed Central ID

PMC2702135

DOI

10.1007/s11517-008-0331-1

Scopus ID

2-s2.0-42549149848   40 Citations

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 alpha-, beta-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 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.

Author List

Liu Y, Li H, Bubolz AH, Zhang DX, Gutterman DD

Authors

David D. Gutterman MD Sr Associate Director, Professor in the Medicine department at Medical College of Wisconsin
David X. Zhang MD, PhD Associate Professor in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Aged
Arterioles
Cells, Cultured
Coronary Circulation
Coronary Vessels
Cytoskeletal Proteins
Cytoskeleton
Endothelium, Vascular
Female
Humans
Male
Vasodilation
jenkins-FCD Prod-482 91ad8a360b6da540234915ea01ff80e38bfdb40a