TY - JOUR
T1 - Cyclic stretch regulates autocrine IGF-I in vascular smooth muscle cells
T2 - Implications in vascular hyperplasia
AU - Standley, Paul R.
AU - Obards, Tamar J.
AU - Martina, Cherie L.
PY - 1999
Y1 - 1999
N2 - -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 serumstarved, 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 GdCla 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. insulin-like growth factor I; restenosis; platelet-derived growth factor; tyrosine kinase
AB - -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 serumstarved, 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 GdCla 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. insulin-like growth factor I; restenosis; platelet-derived growth factor; tyrosine kinase
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U2 - 10.1152/ajpendo.1999.276.4.e697
DO - 10.1152/ajpendo.1999.276.4.e697
M3 - Article
C2 - 10198306
AN - SCOPUS:0032948088
SN - 0002-9513
VL - 276
SP - E697-E705
JO - American Journal of Physiology
JF - American Journal of Physiology
IS - 4 PART 1
ER -