Abstract
We investigated the effects of cyclic stretch on vascular smooth muscle cell (VSMC) alignment and potential overlap of signaling modalities with stretch-induced proliferation. VSMC were subjected to graded stretch (1 Hz at 100-124% of resting length) for 48 h. Graded stretch resulted in graded VSMC alignment from a minimum of completely random orientation to a maximum of ∼80-85° to the stretch vector. Alignment was reversible within 48 h of stretch cessation and independent of signaling modalities mediating stretch-induced proliferation: modulation of IGF-1, MAPK, phosphatidylinositol 3-kinase, tyrosine kinase, and stretch-activated calcium channels did not affect alignment. Nitric oxide (NO) synthase (NOS) blockade uncoupled alignment. Neither the NO donor, cytokine-induced NOS activity, nor L-citrulline affected alignment, but inhibited VSMC proliferation. Therefore, stretch-induced proliferation and alignment are differentially regulated, with NO a common signaling molecule for both. Targeting NOS in states such as restenosis and hypertension may prove to be beneficial.
Original language | English (US) |
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Pages (from-to) | H1907-H1914 |
Journal | American Journal of Physiology - Heart and Circulatory Physiology |
Volume | 283 |
Issue number | 5 52-5 |
DOIs | |
State | Published - Nov 1 2002 |
Keywords
- Cellular alignment
- Migration
- Nitric oxide
- Strain
ASJC Scopus subject areas
- Physiology
- Cardiology and Cardiovascular Medicine
- Physiology (medical)