http://www.loc.gov/mods/v3 http://www.loc.gov/standards/mods/v3/mods-3-2.xsd
Mechanical stretch of vascular smooth muscle cells
a novel in vitro model to characterize phenotypic expression
The occurrence of vascular domains with specific biological and pharmacological characteristics suggests that smooth muscle cells in different arteries may respond differentially to a wide range of environmental stimuli. In addition, the interplay between stretch and the extracellular matrix microenvironment may be critical for the expression of smooth muscle cell phenotypic properties. To determine if some of these vessel-specific differences may be attributable to mechano-sensitive gene regulation, the influence of cyclical stretch on the expression of genes involved in the contractile process was examined. Steady-state levels of actin, alphalb-, and alpha2B-adrenoceptor mRNAs were assessed in subcultured aortic and coronary smooth muscle cells subjected to maximal stretching (24% elongation) and relaxation cycles at a frequency of 120 cycles/min in a Flexercell strain unit for 72 hr. Stretch on an elastin substrate caused reductions in actin isoform and alphalb-adrenergic receptor mRNA levels, however, a marked increase was observed in the alpha2B-adrenergic receptor message. Interestingly, the magnitude of the responses were not identical in aortic and coronary smooth muscle cells. In contrast, stretching on type I collagen was associated with considerably smaller reductions of actin isoform steady-state mRNA levels, no change in alpha1b-adrenergic receptor mRNA levels and a significant reduction in alpha2B-adrenergic receptor gene expression. These observations appear to be specific to the vasculature and not modulated by environmental stress conditions. The influence of the extracellular matrix on the proliferative response to stretch was also tested. Measurements of 3H-thymidine incorporation in aortic smooth muscle cells was decreased on elastin and increased on collagen. In contrast, DNA synthesis in stretched coronary smooth muscle cells was enhanced on elastin yet no change was seen on collagen. Collectively, these data are consistent with the existence of diverse vascular smooth muscle phenotypes found in vivo and suggest that stretch may be involved in the regulation of contractile-related gene expression in vascular smooth muscle cells. We conclude that smooth muscle cell phenotype, as assessed by northern analysis and DNA synthesis, is regulated in a mechano-sensitive manner; and that this response to stretch is influenced by the extracellular matrix.
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