Intracellular Ca2+ stores are essential for injury induced Ca2+ signaling and re-endothelialization

Zhiqiang Zhao, Petr Walczysko, Min Zhao

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Abstract

Endothelialization repairs the lining of damaged vasculature and is a key process in preventing thrombosis and restenosis. It has been demonstrated that extracellular calcium ([Ca2+]o) influx is important for subsequent endothelialization. The role of intracellular Ca2+ stores in mechanical denudation induced intracellular calcium ([Ca2+] i) rise and endothelialization remains to be demonstrated. Using monolayer culture of a human endothelial cell line (human umbilical vein endothelial cell, HUVEC), we investigated [Ca2+]i wave propagation and re-endothelialization following mechanical denudation. Consistent with previous reports for other types of cells, mechanical denudation induces calcium influx, which is essential for [Ca2+]i rise and endothelialization. Moreover, we found that intracellular Ca 2+ stores are also essential for denudation induced [Ca 2+]i wave initiation and propagation, and the subsequent endothelialization. Thapsigargin which depletes intracellular Ca2+ stores completely abolished [Ca2+]i wave generation and endothelialization. Xestospongin C (XeC), which prevents Ca2+ release from intracellular Ca2+ stores by inhibition of inositol 1,4,5-trisphosphate (IP3) receptor, inhibited intercellular Ca 2+ wave generation and endothelialization following denudation. Purinergic signaling through a suramin sensitive mechanism and gap junction communication also contribute to in intercellular Ca2+ wave propagation and re-endothelialization. We conclude that intracellular Ca 2+ stores, in addition to extracellular Ca2+, are essential for intracellular Ca2+ signaling and subsequent endothelialization following mechanical denudation.

Original languageEnglish (US)
Pages (from-to)595-603
Number of pages9
JournalJournal of Cellular Physiology
Volume214
Issue number3
DOIs
StatePublished - Mar 2008

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ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

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