Cyclic stretch regulates autocrine IGF-I in vascular smooth muscle cells

Implications in vascular hyperplasia

Paul R Standley, T. J. Obards, C. L. Martina

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72 Citations (Scopus)

Abstract

Vascular smooth muscle cells (VSMC) subjected to acute or chronic stretch display enhanced growth rates in vitro and in vivo. Clinical examples of vascular hyperplasia (e.g., systolic hypertension and postinjury restenosis) suggest that local insulin-like growth factor I (IGF-I) expression is enhanced. Therefore, we investigated the role of in vitro cyclic stretch on rat VSMC IGF-I secretion and cellular growth. In serum- free medium, cyclic stretch (1 Hz at 120% resting length for 48 h) stimulated thymidine incorporation ~40% above that seen in nonstretched cells. Graded stretch magnitude (100-125% resting length) yielded graded increases in VSMC growth. Exogenous IGF-I increased growth of serum-starved, nonstretched VSMC in a dose-dependent manner, with maximal growth seen with 10-7 M. IGF-I secretion from stretched cells was 20- to 30-fold greater than from those cells cultured in a static environment. Stretch-induced increases in growth were completely blocked on addition of anti-IGF-I and partially blocked with platelet-derived growth factor (PDGF) antibodies and with a tyrosine kinase inhibitor (tyrphostin-1). Finally, blockade of stretch-activated cation channels with GdCl3 profoundly inhibited stretch-induced growth. We conclude that stretch increases VSMC IGF-I secretion and that such autocrine IGF-I is required for stretch-induced growth. PDGF and stretch-sensitive cation channels are likely additional components of a complex pathway that regulates stretch-induced VSMC seen in systolic hypertension and postinjury restenosis.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume276
Issue number4 39-4
StatePublished - 1999
Externally publishedYes

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Insulin-Like Growth Factor I
Vascular Smooth Muscle
Smooth Muscle Myocytes
Hyperplasia
Blood Vessels
Muscle
Cells
Growth
Platelet-Derived Growth Factor
Cations
Tyrphostins
Hypertension
Serum-Free Culture Media
Cell growth
Protein-Tyrosine Kinases
Thymidine
Rats
Display devices
Cultured Cells
Antibodies

Keywords

  • Insulin-like growth factor I
  • Platelet-derived growth factor
  • Restenosis
  • Tyrosine kinase

ASJC Scopus subject areas

  • Physiology
  • Endocrinology
  • Biochemistry
  • Physiology (medical)

Cite this

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title = "Cyclic stretch regulates autocrine IGF-I in vascular smooth muscle cells: Implications in vascular hyperplasia",
abstract = "Vascular smooth muscle cells (VSMC) subjected to acute or chronic stretch display enhanced growth rates in vitro and in vivo. Clinical examples of vascular hyperplasia (e.g., systolic hypertension and postinjury restenosis) suggest that local insulin-like growth factor I (IGF-I) expression is enhanced. Therefore, we investigated the role of in vitro cyclic stretch on rat VSMC IGF-I secretion and cellular growth. In serum- free medium, cyclic stretch (1 Hz at 120{\%} resting length for 48 h) stimulated thymidine incorporation ~40{\%} above that seen in nonstretched cells. Graded stretch magnitude (100-125{\%} resting length) yielded graded increases in VSMC growth. Exogenous IGF-I increased growth of serum-starved, nonstretched VSMC in a dose-dependent manner, with maximal growth seen with 10-7 M. IGF-I secretion from stretched cells was 20- to 30-fold greater than from those cells cultured in a static environment. Stretch-induced increases in growth were completely blocked on addition of anti-IGF-I and partially blocked with platelet-derived growth factor (PDGF) antibodies and with a tyrosine kinase inhibitor (tyrphostin-1). Finally, blockade of stretch-activated cation channels with GdCl3 profoundly inhibited stretch-induced growth. We conclude that stretch increases VSMC IGF-I secretion and that such autocrine IGF-I is required for stretch-induced growth. PDGF and stretch-sensitive cation channels are likely additional components of a complex pathway that regulates stretch-induced VSMC seen in systolic hypertension and postinjury restenosis.",
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T1 - Cyclic stretch regulates autocrine IGF-I in vascular smooth muscle cells

T2 - Implications in vascular hyperplasia

AU - Standley, Paul R

AU - Obards, T. J.

AU - Martina, C. L.

PY - 1999

Y1 - 1999

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