Role of caveolae in shear stress-mediated endothelium-dependent dilation in coronary arteries

Qiang Chai, Xiao Li Wang, Darryl C. Zeldin, Hon Chi Lee

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

Aims: Caveolae are membrane microdomains where important signalling pathways are assembled and molecular effects trans-duced. In this study, we hypothesized that shear stress-mediated vasodilation (SSD) of mouse small coronary arteries (MCA) is caveolae-dependent. Methods and results: MCA (80-150 μm) isolated from wild-type (WT) and caveolin-1 null (Cav-1-/-) mice were subjected to physiological levels of shear stress (1-25 dynes/cm 2) with and without pre-incubation of inhibitors of nitric oxide synthase (L-NAME), cyclooxygenase (indomethacin, INDO), or cytochrome P450 epoxygenase (SKF 525A). SSD was endothelium-depend-entin WT and Cav-1 -/- coronaries but that in Cav-1-/- was significantly diminished compared with WT. Pre-incubation with L-NAME, INDO, or SKF 525A significantly reduced SSD in WT but not in Cav-1-/- mice. Vessels from the soluble epoxide hydrolase null (Ephx2-/-) mice showed enhanced SSD, which was further augmented by the presence of ara-chidonic acid. In donor-detector-coupled vessel experiments, Cav-1-/- donor vessels produced diminished dilation in WT endothelium-denuded detector vessels compared withWTdonor vessels. Shear stress elicited arobust intracellular Ca 2+ increase in vascular endothelial cells isolated from WT but not those from Cav-1-/- mice. Conclusion: Integrity of caveolae is critical for endothelium-dependent SSD in MCA. Cav-1-/- endothelium is deficient in shear stress-mediated generation of vasodilators including NO, prostaglandins, and epoxyeicosatrienoic acids. Caveolae plays a critical role in endothelial signal transduction from shear stress to vasodilator production and release.

Original languageEnglish (US)
Pages (from-to)151-159
Number of pages9
JournalCardiovascular research
Volume100
Issue number1
DOIs
StatePublished - Oct 1 2013

Keywords

  • Calcium
  • Caveolae
  • Coronary artery
  • Shear stress
  • Soluble epoxide hydrolase

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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