Cyclic stretch affects pulmonary endothelial cell control of pulmonary smooth muscle cell growth

Cristhiaan D. Ochoa, Haven Baker, Stephen Hasak, Robina Matyal, Aleya Salam, Charles A. Hales, William Hancock, Deborah A. Quinn

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Endothelial cells are subjected to mechanical forces in the form of cyclic stretch resulting from blood pulsatility. Pulmonary artery endothelial cells (PAECs) produce factors that stimulate and inhibit pulmonary artery smooth muscle cell (PASMC) growth. We hypothesized that PAECs exposed to cyclic stretch secrete proteins that inhibit PASMC growth. Media from PAECs exposed to cyclic stretch significantly inhibited PASMC growth in a time-dependent manner. Lyophilized material isolated from stretched PAEC-conditioned media significantly inhibited PASMC growth in a dose-dependent manner. This inhibition was reversed by trypsin inactivation, which is consistent with the relevant factor being a protein(s). To identify proteins that inhibited cell growth in conditioned media from stretched PAECs, we used proteomic techniques and found that thrombospondin (TSP)-1, a natural antiangiogenic factor, was up-regulated by stretch. In vitro, exogenous TSP-1 inhibited PASMC growth. TSP-1-blocking antibodies reversed conditionedmedia-induced inhibition of PASMC growth. Cyclic stretched PAECs secrete protein(s) that inhibit PASMC proliferation. TSP-1 may be, at least in part, responsible for this inhibition. The complete identification and understanding of the secreted proteome of stretched PAECs may lead to new insights into the pathophysiology of pulmonary vascular remodeling.

Original languageEnglish (US)
Pages (from-to)105-112
Number of pages8
JournalAmerican journal of respiratory cell and molecular biology
Volume39
Issue number1
DOIs
Publication statusPublished - Jul 1 2008
Externally publishedYes

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Keywords

  • Cyclic stretch
  • Proteomics
  • Pulmonary endothelium
  • Smooth muscle cells growth
  • Thrombospondin-1

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

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