Activation of mitogenic and antimitogenic pathways in cyclically stretched arterial smooth muscle

Paul R. Standley, Melinda A. Stanley, P. Senechal

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

Biophysical forces regulate vascular smooth muscle cell (VSMC) physiology and evoke vascular remodeling. Two VSMC autocrine molecules, insulin-like growth factor I (IGF-I) and nitric oxide (NO), are implicated in remodeling attributable to VSMC hyperplasia. We investigated the role of in vitro cyclic stretch on rat VSMC IGF-I, NO, and cellular growth. Cyclic stretch (1 Hz at 120% resting length for 48 h) stimulated VSMC proliferation 2.5-fold vs. unstretched cells and was accompanied by a 1.8-fold increase in VSMC IGF-I secretion. Despite activation of this proliferative pathway, cyclic stretch induced inducible (i) nitric oxide synthase (NOS) expression and a twofold increase in NO secretion, a molecule with documented antiproliferative effects. Cytokine treatment enhanced iNOS expression and NO secretion while inhibiting vascular growth by ≈50% in static cells. Cytokine treatment of stretched VSMC enhanced NO secretion 2.5-fold while inhibiting growth by ≈80%. Exogenous IGF-I increased NOS activity 1.5-fold and NO secretion 8.5-fold in static cells. In turn, iNOS inhibition increased IGF-I secretion 1.6-fold and enhanced VSMC growth 1.6-fold in stretched cells. An NO donor (sodium nitroprusside) similarly inhibited VSMC proliferation in static (24%) and stretched (50%) VSMC while also inhibiting IGF-I secretion from stretched cells by ≈35%. Thus cyclic stretch stimulates mitogenic (IGF-I) and antimitogenic (NO) pathways in VSMC. These two molecules regulate each other's secretory rates, providing tight regulation of VSMC proliferation. These data may have profound implications in understanding vascular growth alterations in vascular injury and hypertension.

Original languageEnglish (US)
Pages (from-to)E1165-E1171
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume281
Issue number6 44-6
DOIs
StatePublished - Jan 1 2001
Externally publishedYes

Keywords

  • Hyperplasia
  • Insulin-like growth factor
  • Nitric oxide
  • Vascular smooth muscle

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

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