Arteriosclerosis and Thrombosis, Vol 11, 892-902, Copyright © 1991 by American Heart Association

ARTICLES

Effects of transforming growth factor-beta 1 on human arterial smooth muscle cells in vitro

S Bjorkerud
Department of Pathology I, University of Gothenburg, Sweden.

Control of the thickness of the arterial wall is critical, as excessive overgrowth of constituent smooth muscle cells (SMCs) may interfere with blood flow. Effects on SMCs in vitro of several growth factors that are present in blood and/or that are produced endogenously in the arterial wall under certain conditions suggest that influences of endocrine, paracrine, and autocrine nature from stimulating and inhibiting factors may control the smooth muscle tissue mass in the artery. This possibility was explored further by investigating the degree of myodifferentiation in terms of the presence of differentiation-specific filamentous alpha-smooth muscle actin and growth, as measured by the synthesis of DNA and cell number, of SMCs as influenced by their exposure to the mitogens, platelet-derived growth factor and epidermal growth factor, and the bifunctional growth factor, transforming growth factor-beta 1 (TGF-beta 1). Exposure to TGF-beta 1 markedly enhanced differentiation-specific filamentous alpha-smooth muscle actin. This effect did not require arrest of growth, which speaks against a direct causal relation between loss of myodifferentiation (modulation) and multiplication. When quiescent cultures were exposed to TGF-beta 1, alpha-smooth muscle actin was further increased, indicating a more specific differentiation-promoting effect by TGF-beta 1 than mere inhibition of growth. Exposure to TGF-beta 1 also increased spreading, which occurred in parallel with increased filamentous alpha-smooth muscle actin and appearance of stress fibers. Exposure to platelet- derived growth factor under serum-free conditions and to epidermal growth factor in cultures exposed to serum markedly decreased the number of alpha-actin-positive SMCs, indicating a dedifferentiating effect by these mitogens. Exposure of SMCs to TGF-beta 1 under serum- free conditions had pronounced effects on growth, with a concentration- dependent inhibition of platelet-derived growth factor-induced DNA synthesis and cell multiplication. The basal synthesis of DNA in the absence of added growth factors was also greatly inhibited. With serum- free cultures, some loss of cells occurred even with very low concentrations of TGF-beta 1 (5 pg/ml), against which platelet-derived growth factor or a dense cultural state had a protective effect. Enhancement of cell multiplication was not detected for cultivated human SMCs exposed to TGF-beta 1, irrespective of culture density, in contrast to that reported for dense cultures of rat SMCs. TGF-beta 1 is present in and may be released from platelets in situations that promote platelet adherence such as endothelial injury; TGF-beta 1 may also be released from activated macrophages and T lymphocytes either during an immune reaction or inflammation or from the endothelium.(ABSTRACT TRUNCATED AT 400 WORDS)

This article has been cited by other articles:

				P. T.G. Bot, I. E. Hoefer, J. P.G. Sluijter, P. van Vliet, A. M. Smits, F. Lebrin, F. Moll, J.-P. de Vries, P. Doevendans, J. J. Piek, et al. Increased Expression of the Transforming Growth Factor-{beta} Signaling Pathway, Endoglin, and Early Growth Response-1 in Stable Plaques Stroke, February 1, 2009; 40(2): 439 - 447. [Abstract] [Full Text] [PDF]

				Z. Gong and L. E. Niklason Small-diameter human vessel wall engineered from bone marrow-derived mesenchymal stem cells (hMSCs) FASEB J, June 1, 2008; 22(6): 1635 - 1648. [Abstract] [Full Text] [PDF]

				T. Korff, K. Aufgebauer, and M. Hecker Cyclic Stretch Controls the Expression of CD40 in Endothelial Cells by Changing Their Transforming Growth Factor-{beta}1 Response Circulation, November 13, 2007; 116(20): 2288 - 2297. [Abstract] [Full Text] [PDF]

				D. J. Grainger TGF-{beta} and atherosclerosis in man Cardiovasc Res, May 1, 2007; 74(2): 213 - 222. [Abstract] [Full Text] [PDF]

				M. D. Jarvis, M. T. Rademaker, L. J. Ellmers, M. J. Currie, J. L. McKenzie, B. R. Palmer, C. M. Frampton, A. M. Richards, and V. A. Cameron Comparison of infarct-derived and control ovine cardiac myofibroblasts in culture: response to cytokines and natriuretic peptide receptor expression profiles. Am J Physiol Heart Circ Physiol, October 1, 2006; 291(4): H1952 - H1958. [Abstract] [Full Text] [PDF]

				G. Otsuka, R. Agah, A. D. Frutkin, T. N. Wight, and D. A. Dichek Transforming Growth Factor Beta 1 Induces Neointima Formation Through Plasminogen Activator Inhibitor-1-Dependent Pathways Arterioscler Thromb Vasc Biol, April 1, 2006; 26(4): 737 - 743. [Abstract] [Full Text] [PDF]

				A. M. Goldsmith, J. K. Bentley, L. Zhou, Y. Jia, K. N. Bitar, D. C. Fingar, and M. B. Hershenson Transforming Growth Factor-beta Induces Airway Smooth Muscle Hypertrophy Am. J. Respir. Cell Mol. Biol., February 1, 2006; 34(2): 247 - 254. [Abstract] [Full Text] [PDF]

				R. A. Deaton, C. Su, T. G. Valencia, and S. R. Grant Transforming Growth Factor-{beta}1-induced Expression of Smooth Muscle Marker Genes Involves Activation of PKN and p38 MAPK J. Biol. Chem., September 2, 2005; 280(35): 31172 - 31181. [Abstract] [Full Text] [PDF]

				K.-G. Shyu, Y.-M. Chao, B.-W. Wang, and P. Kuan Regulation of Discoidin Domain Receptor 2 by Cyclic Mechanical Stretch in Cultured Rat Vascular Smooth Muscle Cells Hypertension, September 1, 2005; 46(3): 614 - 621. [Abstract] [Full Text] [PDF]

				S. Sinha, M. H. Hoofnagle, P. A. Kingston, M. E. McCanna, and G. K. Owens Transforming growth factor-{beta}1 signaling contributes to development of smooth muscle cells from embryonic stem cells Am J Physiol Cell Physiol, December 1, 2004; 287(6): C1560 - C1568. [Abstract] [Full Text] [PDF]

				J. G. Elliot, C. M. Jensen, S. Mutavdzic, J. P. Lamb, N. G. Carroll, and A. L. James Aggregations of Lymphoid Cells in the Airways of Nonsmokers, Smokers, and Subjects with Asthma Am. J. Respir. Crit. Care Med., March 15, 2004; 169(6): 712 - 718. [Abstract] [Full Text] [PDF]

				D. J. Grainger Transforming Growth Factor {beta} and Atherosclerosis: So Far, So Good for the Protective Cytokine Hypothesis Arterioscler Thromb Vasc Biol, March 1, 2004; 24(3): 399 - 404. [Abstract] [Full Text]

				M. Mori, H. Kida, H. Morishita, S. Goya, H. Matsuoka, T. Arai, T. Osaki, I. Tachibana, S. Yamamoto, M. Sakatani, et al. Microsatellite Instability in Transforming Growth Factor-{beta}1 Type II Receptor Gene in Alveolar Lining Epithelial Cells of Idiopathic Pulmonary Fibrosis Am. J. Respir. Cell Mol. Biol., April 1, 2001; 24(4): 398 - 404. [Abstract] [Full Text]

				X. Ma, M. Labinaz, J. Goldstein, H. Miller, W. J. Keon, M. Letarte, and E. O'Brien Endoglin Is Overexpressed After Arterial Injury and Is Required for Transforming Growth Factor-{beta}-Induced Inhibition of Smooth Muscle Cell Migration Arterioscler Thromb Vasc Biol, December 1, 2000; 20(12): 2546 - 2552. [Abstract] [Full Text] [PDF]

				A.-C. Desfaits, J. Raymond, and J. P. Muizelaar Growth Factors Stimulate Neointimal Cells In Vitro and Increase the Thickness of the Neointima Formed at the Neck of Porcine Aneurysms Treated by Embolization • Editorial Comment Stroke, February 1, 2000; 31(2): 498 - 507. [Abstract] [Full Text] [PDF]

				D. Grainger, D. Mosedale, J. Metcalfe, and E. Bottinger Dietary fat and reduced levels of TGFbeta1 act synergistically to promote activation of the vascular endothelium and formation of lipid lesions J. Cell Sci., January 7, 2000; 113(13): 2355 - 2361. [Abstract] [PDF]

				J. B. Hoying, M. Yin, R. Diebold, I. Ormsby, A. Becker, and T. Doetschman Transforming Growth Factor beta 1 Enhances Platelet Aggregation through a Non-transcriptional Effect on the Fibrinogen Receptor J. Biol. Chem., October 22, 1999; 274(43): 31008 - 31013. [Abstract] [Full Text] [PDF]

				H. Abe, N. Iehara, K. Utsunomiya, T. Kita, and T. Doi A Vitamin D Analog Regulates Mesangial Cell Smooth Muscle Phenotypes in a Transforming Growth Factor-beta Type II Receptor-mediated Manner J. Biol. Chem., July 23, 1999; 274(30): 20874 - 20878. [Abstract] [Full Text] [PDF]

				T. Christen, M.-L. Bochaton-Piallat, P. Neuville, S. Rensen, M. Redard, G. van Eys, and G. Gabbiani Cultured Porcine Coronary Artery Smooth Muscle Cells : A New Model With Advanced Differentiation Circ. Res., July 9, 1999; 85(1): 99 - 107. [Abstract] [Full Text] [PDF]

				P. D. Arora, N. Narani, and C. A. G. McCulloch The Compliance of Collagen Gels Regulates Transforming Growth Factor-ß Induction of {alpha}-Smooth Muscle Actin in Fibroblasts Am. J. Pathol., March 1, 1999; 154(3): 871 - 882. [Abstract] [Full Text] [PDF]

				A. M. Romanic, A. J. Arleth, R. N. Willette, and E. H. Ohlstein Factor XIIIa Cross-links Lipoprotein(a) With Fibrinogen and Is Present in Human Atherosclerotic Lesions Circ. Res., August 10, 1998; 83(3): 264 - 269. [Abstract] [Full Text] [PDF]

				S. McKay, J. C. de Jongste, P. R. Saxena, and H. S. Sharma Angiotensin II Induces Hypertrophy of Human Airway Smooth Muscle Cells: Expression of Transcription Factors and Transforming Growth Factor-beta 1 Am. J. Respir. Cell Mol. Biol., June 1, 1998; 18(6): 823 - 833. [Abstract] [Full Text]

				S. S. Patel, R. Thiagarajan, J. T. Willerson, and E. T. H. Yeh Inhibition of {alpha}4 Integrin and ICAM-1 Markedly Attenuate Macrophage Homing to Atherosclerotic Plaques in ApoE-Deficient Mice Circulation, January 13, 1998; 97(1): 75 - 81. [Abstract] [Full Text] [PDF]

				D. Grainger, J. Metcalfe, A. Grace, and D. Mosedale Transforming growth factor-beta dynamically regulates vascular smooth muscle differentiation in vivo J. Cell Sci., January 10, 1998; 111(19): 2977 - 2988. [Abstract] [PDF]

				M. B. Hautmann, M. M. Thompson, E. A. Swartz, E. N. Olson, and G. K. Owens Angiotensin II–Induced Stimulation of Smooth Muscle {alpha}-Actin Expression by Serum Response Factor and the Homeodomain Transcription Factor MHox Circ. Res., October 19, 1997; 81(4): 600 - 610. [Abstract] [Full Text]

				M. B. Hautmann, C. S. Madsen, and G. K. Owens A Transforming Growth Factor beta (TGFbeta ) Control Element Drives TGFbeta -induced Stimulation of Smooth Muscle alpha -Actin Gene Expression in Concert with Two CArG Elements J. Biol. Chem., April 18, 1997; 272(16): 10948 - 10956. [Abstract] [Full Text] [PDF]

				J. Reckless, J. C. Metcalfe, and D. J. Grainger Tamoxifen Decreases Cholesterol Sevenfold and Abolishes Lipid Lesion Development in Apolipoprotein E Knockout Mice Circulation, March 18, 1997; 95(6): 1542 - 1548. [Abstract] [Full Text]

				J. Waltenberger, M. L. Akyurek, M. Aurivillius, A. Wanders, E. Larsson, B. Fellstrom, and K. Funa Ischemia-Induced Transplant Arteriosclerosis in the Rat: Induction of Peptide Growth Factor Expression Arterioscler Thromb Vasc Biol, December 1, 1996; 16(12): 1516 - 1523. [Abstract] [Full Text]

				B. Bjorkerud and S. Bjorkerud Contrary Effects of Lightly and Strongly Oxidized LDL With Potent Promotion of Growth Versus Apoptosis on Arterial Smooth Muscle Cells, Macrophages, and Fibroblasts Arterioscler Thromb Vasc Biol, March 1, 1996; 16(3): 416 - 424. [Abstract] [Full Text]

				D. Grainger, H. Kirschenlohr, J. Metcalfe, P. Weissberg, D. Wade, and R. Lawn Proliferation of human smooth muscle cells promoted by lipoprotein(a) Science, June 11, 1993; 260(5114): 1655 - 1658. [Abstract] [PDF]

				E. Arciniegas, A. B. Sutton, T. D. Allen, and A. M. Schor Transforming growth factor beta 1 promotes the differentiation of endothelial cells into smooth muscle-like cells in vitro J. Cell Sci., October 1, 1992; 103(2): 521 - 529. [Abstract] [PDF]