Summary
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. 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 actin isoform and α1B-adrenoceptor genes was examined in aortic and coronary smooth muscle cells. Cells were seeded on an elastin substrate and subjected to maximal stretching (24% elongation) and relaxation cycles at a frequency of 120 cycles/min in a Flexercell strain unit for 72 h. Total RNA was extracted and hybridized to radiolabeled cDNA probes to assess gene expression. Stretch caused a greater reduction of actin isoform mRNA levels in aortic smooth muscle cells as compared to cells from the coronary artery. Steady-state mRNA levels of α1B -adrenoceptor were also decreased by cyclical stretch in both cell types but the magnitude of the response was greater in coronary smooth muscle cells. No changes in α1B-adrenoceptor or β/γ-actin steady-state mRNA levels were observed in H4IIE cells, a nonvascular, immortalized cell line. The relative gene expression of heat shock protein 70 was not influenced by the cyclic stretch regimen in any of these cell types. These results suggest that stretch may participate in the regulation of gene expression in vascular smooth muscle cells and that this response exhibits some degree of cell-specificity.
Similar content being viewed by others
References
Adams, J. C.; Watt, F. M. Fibronectin inhibits the terminal differentiation of human keratinocytes. Nature (Lond.) 340:307–309; 1989.
Allen, L. F.; Lefkowitz, R. J.; Caron, M. G., et al. G-protein-coupled protooncogenes: constitutively activating mutation of the α1B-adrenergic receptor enhances mitogenesis and tumorigenicity. Proc. Natl. Acad. Sci. USA 88:11354–11358; 1991.
Banes, A. J.; Link, G. W., Jr.; Gilbert, J. W., et al. Culturing cells in a mechanically active environment. Amer. Biotech. Lab. 8(7):12–22; 1990.
Bevan, J. A.; Bevan, R. D.; Chang, P. C., et al. Analysis of changes in reactivity of rabbit arteries and veins two weeks after induction of hypertension by coarctation of the abdominal aorta. Circ. Res. 37:183–190; 1975.
Bodin, P.; Bailey, D.; Burnstock, G. Increased flow-induced ATP release from vascular endothelial cells but not smooth muscle cells. Br. J. Pharmacol. 103:1203–1205; 1991.
Bowes, R. C., III; Ramos, K. S. Differential phospholipid metabolism in rat aortic smooth muscle cells of varying proliferative potential upon long term exposure to phorbol 12-myristate-13-acetate. Chem. Biol. Interactions 86(7):213–228; 1993.
Buck, R. C. Behavior of vascular smooth muscle cells during repeated stretching of the substratum in vitro. Atherosclerosis 46:217–223; 1983.
Burn, P. Amphitropic proteins: a new class of membrane proteins. Trends Biochem. Sci. 13:79–83; 1990.
Burridge, K.; Fath, K. Focal contacts: transmembrane links between the extracellular matrix and the cytoskeleton. BioEssays 10:104–108; 1989.
Chilian, W. M. Functional distribution of α1- and α2- adrenergic receptors in the coronary microcirculation. Circulation 84(5):2108–2122; 1991.
Chilian, W. M.; Layne, S. M.; Eastham, C. I., et al. Heterogeneous micro-vascular coronary α-adrenergic vasoconstriction. Circ. Res. 64:376–388; 1989.
Coleridge, H. M.; Coleridge, J. C. G.; Poore, E. R., et al. Aortic wall properties and baroreceptor behavior at normal arterial pressure and in acute hypertensive resetting in dogs. J. Physiol. 350:309–326; 1984.
Dartsch, P. C.; Haemmerle, H.; Betz, E. Orientation of cultured arterial smooth muscle cells growing on cyclically stretched substrates. Acta Anat. 125:108–113; 1986.
Davies, P. F.; Tripathi, S. C. Mechanical stress mechanisms and the cell. An endothelial paradigm. Circ. Res. 72:239–245; 1993.
DeMey, J. G. R.; Uitendaal, M. P.; Boonen, H. C. M., et al. Growth responses in isolated elastic, muscular and resistance-sized arterial segments of rat. Blood Vessels 28:372–385; 1991.
Faber, J. E. In situ analysis of α-adrenoceptors on arteriolar and venular smooth muscle in rat skeletal muscle microcirculation. Circ. Res. 62:37–50; 1988.
Fernandez, R. J. L.; Ben-Ze’ev, A. Regulation of fibronectin, integrin and cytoskeletal expression in differentiating adipocytes: inhibition by extracellular matrix and polylysine. Differentiation 42:65–74; 1989.
Grosso, L. E.; Park, P. W.; Mecham, R. P. Characterization of a putative clone for the 67-kilodalton elastin/laminin receptor suggests that it encodes a cytoplasmic protein rather than a cell surface receptor. Biochemistry 30:3346–3350; 1991.
Hedin, U.; Bottger, B. A.; Luthman, J., et al. A substrate of the cell-attachment sequence of fibronectin (Arg-Gly-Asp-Ser) is sufficient to promote transition of arterial smooth muscle cells from a contractile to a synthetic phenotype. Dev. Biol. 133:489–501; 1989.
Hedin, U.; Sjolund, M.; Hultgardh-Nilsson, A., et al. Changes in expression and organization of smooth-muscle-specific α actin during fibronectin-mediated modulation of arterial smooth muscle cell phenotype. Differentiation 44:222–231; 1990.
Hynes, R. O. Integrins: versatility, modulation, and signaling in cell adhesion. Cell 69:11–25; 1992.
Ingber, D. E. Cellular tensegrity: defining new rules of biological design that govern the cytoskeleton. J. Cell Sci. 104:613–627; 1991.
Ingber, D. E.; Jamieson, J. D. Cells as tensegrity structures: architectural regulation of histodifferentiation by physical forces transduced over basement membrane. In: Andersson, L. C.; Gahmberg, C. G.; Ekblom, P., eds. Gene expression during normal and malignant differentiation. Academic Press; 1985:13–32.
Kocher, O.; Skalli, O.; Cerutti, D., et al Cytoskeletal features of rat aortic cells during development. Circ. Res. 56:829–838; 1985.
Leung, D. Y. M.; Glagov, S.; Matthews, M. B. Cyclic stretching stimulates synthesis of matrix components by arterial smooth muscle cells in vitro. Science 191:475–477; 1975.
Majesky, M. W.; Daemen, M. J.; Schwartz, S. M. α1-adrenergic stimulation of platelet-derived growth factor A-chain gene expression in rat aorta. J. Biol. Chem. 265:1082–1088; 1990.
Mecham, R. P. Elastin synthesis and fiber assembly. Ann. NY Acad. Sci. 624:137–146; 1991.
Mecham, R. P.; Whitehouse, L. A.; Wrenn, D. S., et al. Smooth muscle-mediated connective tissue remodeling in pulmonary hypertension. Science 237:423–426; 1987.
Mills, I.; Letsou, G.; Rabban, J., et al. Mechanosensitive adenylate cyclase activity in coronary vascular smooth muscle cells. Biochem. Biophys. Res. Comm. 171(1):143–147; 1990.
Murray, T. R.; Marshall, B. E.; Macarak, E. J. Contraction of vascular smooth muscle in cell culture. J. Cell. Physiol. 143:26–38; 1990.
Nakaki, T.; Nakayama, M.; Yamamoto, S., et al. α1-adrenergic stimulation and β2-adrenergic inhibition of DNA synthesis in vascular smooth muscle cells. Mol. Pharmacol. 37:30–36; 1989.
Nigg, E. A. Mechanisms of signal transduction to the cell nucleus. Adv. Cancer Res. 55:271–310; 1990.
Nomura, K.; Teraoka, H.; Arita, H., et al. Disorganization of microfilaments is accompanied by downregulation of alpha-smooth muscle actin isoform mRNA level in cultured vascular smooth muscle cells. J. Biochem. (Tokyo) 112(1):102–106; 1992.
Owens, G. K.; Thompson, M. M. Developmental changes in isoactin expression in rat aortic smooth muscle cells in vivo. J. Biol. Chem. 261(28):13373–13380; 1986.
Ramos, K.; Cox, L. R. Primary cultures of rat aortic endothelial and smooth muscle cells: an in vitro model to study xenobiotic-induced vascular cytotoxicity. In Vitro Cell. Dev. Biol. 23:288–296; 1987.
Robert, L.; Jacob, M. P.; Fulop, T., et al. Elastonectin and the elastin receptor. Pathol. Biol. 37(6):736–741; 1989.
Seidel, C. L.; Schildmeyer, L. A. Vascular smooth muscle adaptation to increased load. Annu. Rev. Physiol. 49:489–499; 1987.
Sottiurai, V. S.; Kollros, P.; Glagow, S., et al. Morphologic alteration of cultured arterial smooth muscle cells by cyclic stretching. J. Surg. Res. 35:490–497; 1983.
Sterpetti, A. V.; Cucina, A.; D’Angelo, L. S., et al. Shear stress modulates the proliferation rate, protein synthesis, and mitogenic activity of arterial smooth muscle cells. Surgery 113(6):691–699; 1993.
Sumpio, B. E.; Banes, A. J. Response of porcine aortic smooth muscle cells to cyclic tensional deformation in culture. J. Surg. Res. 44:696–701; 1988.
Sumpio, B. E.; Banes, A. J.; Link, W. G., et al. Enhanced collagen production by smooth muscle cells during repetitive mechanical stretching. Arch. Surg. 123:1233–1236; 1988.
Terracio, L.; Tingstrom, A.; Peters, W. H., et al. A potential role for mechanical stimulation in cardiac development. Ann. NY Acad. Sci. 588:48–60; 1990.
Turner, C. E.; Glenney, J. R.; Burridge, K. Paxillin: a new vinculin-binding protein present in focal adhesions. J. Cell. Biol. 111:1059–1068; 1990.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Lundberg, M.S., Sadhu, D.N., Grumman, V.E. et al. Actin isoform and α1B-adrenoceptor gene expression in aortic and coronary smooth muscle is influenced by cyclical stretch. In Vitro Cell Dev Biol - Animal 31, 595–600 (1995). https://doi.org/10.1007/BF02634312
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02634312