This Article Order Full text via Infotrieve Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Donovan, M. J. Articles by Parada, L. Search for Related Content PubMed PubMed Citation Articles by Donovan, M. J. Articles by Parada, L.

American Journal of Pathology, Vol 147, 309-324, Copyright © 1995 by American Society for Investigative Pathology

REGULAR ARTICLES

Neurotrophin and neurotrophin receptors in vascular smooth muscle cells. Regulation of expression in response to injury

MJ Donovan, RC Miranda, R Kraemer, TA McCaffrey, L Tessarollo, D Mahadeo, S Sharif, DR Kaplan, P Tsoulfas and L Parada
Department of Pathology, Children's Hospital, Boston, Massachusetts, USA.

The neurotrophins, a family of related polypeptide growth factors including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and neurotrophin (NT)-3 and NT-4/5 promote the survival and differentiation of distinctive sets of embryonic neurons. Here we define a new functional role for neurotrophins, as autocrine or local paracrine mediators of vascular smooth muscle cell migration. We have identified neurotrophins, and their cognate receptors, the trk tyrosine kinases, in human and rat vascular smooth muscle cells in vivo. In vitro, cultured human smooth muscle cells express BDNF; NT-3; and trk A, B, and C. Similarly, rat smooth muscle cells expressed all three trk receptors as well as all four neurotrophins. Moreover, NGF induces cultured human smooth muscle cell migration at subnanomolar concentrations. In the rat aortic balloon deendothelialization model of vascular injury, the expression of NGF, BNDF, and their receptors trk A and trk B increased dramatically in the area of injury within 3 days and persisted during the formation of the neointima. In human coronary atherosclerotic lesions, BDNF, NT-3, and NT-4/5, and the trk B and trk C receptors could be demonstrated in smooth muscle cells. These findings suggest that neurotrophins play an important role in regulating the response of vascular smooth muscle cells to injury.

This article has been cited by other articles:

				S. Begliuomini, E. Lenzi, F. Ninni, E. Casarosa, S. Merlini, N. Pluchino, V. Valentino, S. Luisi, M. Luisi, and A. R Genazzani Plasma brain-derived neurotrophic factor daily variations in men: correlation with cortisol circadian rhythm J. Endocrinol., May 1, 2008; 197(2): 429 - 435. [Abstract] [Full Text] [PDF]

				D. H. Damon TH and NPY in sympathetic neurovascular cultures: role of LIF and NT-3 Am J Physiol Cell Physiol, January 1, 2008; 294(1): C306 - C312. [Abstract] [Full Text] [PDF]

				S. Begliuomini, E. Casarosa, N. Pluchino, E. Lenzi, M. Centofanti, L. Freschi, M. Pieri, A.D. Genazzani, S. Luisi, and A. R. Genazzani Influence of endogenous and exogenous sex hormones on plasma brain-derived neurotrophic factor Hum. Reprod., April 1, 2007; 22(4): 995 - 1002. [Abstract] [Full Text] [PDF]

				D. H. Damon Vascular endothelial-derived semaphorin 3 inhibits sympathetic axon growth Am J Physiol Heart Circ Physiol, March 1, 2006; 290(3): H1220 - H1225. [Abstract] [Full Text] [PDF]

				D. Cai, J. M. Holm, I. J. Duignan, J. Zheng, M. Xaymardan, A. Chin, V. L. T. Ballard, J. N. Bella, and J. M. Edelberg BDNF-mediated enhancement of inflammation and injury in the aging heart Physiol Genomics, February 23, 2006; 24(3): 191 - 197. [Abstract] [Full Text] [PDF]

				R. Kraemer, P. J. Baker, K. C. Kent, Y. Ye, J. J. Han, R. Tejada, M. Silane, R. Upmacis, R. Deeb, Y. Chen, et al. Decreased Neurotrophin TrkB Receptor Expression Reduces Lesion Size in the Apolipoprotein E-Null Mutant Mouse Circulation, December 6, 2005; 112(23): 3644 - 3653. [Abstract] [Full Text] [PDF]

				N. Wagner, K.-D. Wagner, H. Theres, C. Englert, A. Schedl, and H. Scholz Coronary vessel development requires activation of the TrkB neurotrophin receptor by the Wilms' tumor transcription factor Wt1 Genes & Dev., November 1, 2005; 19(21): 2631 - 2642. [Abstract] [Full Text] [PDF]

				J. Ejiri, N. Inoue, S. Kobayashi, R. Shiraki, K. Otsui, T. Honjo, M. Takahashi, Y. Ohashi, S. Ichikawa, M. Terashima, et al. Possible Role of Brain-Derived Neurotrophic Factor in the Pathogenesis of Coronary Artery Disease Circulation, October 4, 2005; 112(14): 2114 - 2120. [Abstract] [Full Text] [PDF]

				E. Lobos, C. Gebhardt, A. Kluge, and K. Spanel-Borowski Expression of Nerve Growth Factor (NGF) Isoforms in the Rat Uterus during Pregnancy: Accumulation of Precursor proNGF Endocrinology, April 1, 2005; 146(4): 1922 - 1929. [Abstract] [Full Text] [PDF]

				H. Kim, Q. Li, B. L. Hempstead, and J. A. Madri Paracrine and Autocrine Functions of Brain-derived Neurotrophic Factor (BDNF) and Nerve Growth Factor (NGF) in Brain-derived Endothelial Cells J. Biol. Chem., August 6, 2004; 279(32): 33538 - 33546. [Abstract] [Full Text] [PDF]

				R. Rajagopal, Z.-Y. Chen, F. S. Lee, and M. V. Chao Transactivation of Trk Neurotrophin Receptors by G-Protein-Coupled Receptor Ligands Occurs on Intracellular Membranes J. Neurosci., July 28, 2004; 24(30): 6650 - 6658. [Abstract] [Full Text] [PDF]

				Z.-Y. Chen, P. D. Patel, G. Sant, C.-X. Meng, K. K. Teng, B. L. Hempstead, and F. S. Lee Variant Brain-Derived Neurotrophic Factor (BDNF) (Met66) Alters the Intracellular Trafficking and Activity-Dependent Secretion of Wild-Type BDNF in Neurosecretory Cells and Cortical Neurons J. Neurosci., May 5, 2004; 24(18): 4401 - 4411. [Abstract] [Full Text] [PDF]

				E. Ghinelli, J. Johansson, J. D. Rios, L.-L. Chen, D. Zoukhri, R. R. Hodges, and D. A. Dartt Presence and Localization of Neurotrophins and Neurotrophin Receptors in Rat Lacrimal Gland Invest. Ophthalmol. Vis. Sci., August 1, 2003; 44(8): 3352 - 3357. [Abstract] [Full Text] [PDF]

				R. Kraemer Reduced Apoptosis and Increased Lesion Development in the Flow-Restricted Carotid Artery of p75NTR-Null Mutant Mice Circ. Res., September 20, 2002; 91(6): 494 - 500. [Abstract] [Full Text] [PDF]

				S. Capsoni, S. Giannotta, and A. Cattaneo Nerve growth factor and galantamine ameliorate early signs of neurodegeneration in anti-nerve growth factor mice PNAS, September 17, 2002; 99(19): 12432 - 12437. [Abstract] [Full Text] [PDF]

				R. Lee, P. Kermani, K. K. Teng, and B. L. Hempstead Regulation of Cell Survival by Secreted Proneurotrophins Science, November 30, 2001; 294(5548): 1945 - 1948. [Abstract] [Full Text] [PDF]

				D. H. Damon NGF-independent survival of postganglionic sympathetic neurons in neuronal-vascular smooth muscle cocultures Am J Physiol Heart Circ Physiol, April 1, 2001; 280(4): H1722 - H1728. [Abstract] [Full Text] [PDF]

				P. Stawowy, J. Marcinkiewicz, K. Graf, N. G. Seidah, M. Chrétien, E. Fleck, and M. Marcinkiewicz Selective Expression of the Proprotein Convertases Furin, PC5, and PC7 in Proliferating Vascular Smooth Muscle Cells of the Rat Aorta In Vitro J. Histochem. Cytochem., March 1, 2001; 49(3): 323 - 332. [Abstract] [Full Text]

				L. Campagnolo, M.A. Russo, A. Puglianiello, A. Favale, and G. Siracusa Mesenchymal Cell Precursors of Peritubular Smooth Muscle Cells of the Mouse Testis Can Be Identified by the Presence of the p75 Neurotrophin Receptor Biol Reprod, February 1, 2001; 64(2): 464 - 472. [Abstract] [Full Text]

				S. Wang, P. Bray, T. McCaffrey, K. March, B. L. Hempstead, and R. Kraemer p75NTR Mediates Neurotrophin-Induced Apoptosis of Vascular Smooth Muscle Cells Am. J. Pathol., October 1, 2000; 157(4): 1247 - 1258. [Abstract] [Full Text] [PDF]

				I. Das, J. R. Sparrow, M. I. Lin, E. Shih, T. Mikawa, and B. L. Hempstead Trk C Signaling Is Required for Retinal Progenitor Cell Proliferation J. Neurosci., April 15, 2000; 20(8): 2887 - 2895. [Abstract] [Full Text] [PDF]

				M. Donovan, M. Lin, P Wiegn, T Ringstedt, R Kraemer, R Hahn, S Wang, C. Ibanez, S Rafii, and B. Hempstead Brain derived neurotrophic factor is an endothelial cell survival factor required for intramyocardial vessel stabilization Development, January 11, 2000; 127(21): 4531 - 4540. [Abstract] [PDF]

				S. Sanovic, D. P. Lamb, and M. G. Blennerhassett Damage to the Enteric Nervous System in Experimental Colitis Am. J. Pathol., October 1, 1999; 155(4): 1051 - 1057. [Abstract] [Full Text] [PDF]

				M. Lommatzsch, A. Braun, A. Mannsfeldt, V. A. Botchkarev, N. V. Botchkareva, R. Paus, A. Fischer, G. R. Lewin, and H. Renz Abundant Production of Brain-Derived Neurotrophic Factor by Adult Visceral Epithelia : Implications for Paracrine and Target-Derived NeurotrophicFunctions Am. J. Pathol., October 1, 1999; 155(4): 1183 - 1193. [Abstract] [Full Text] [PDF]

				M.A. Russo, M.L. Giustizieri, A. Favale, M.C. Fantini, L. Campagnolo, D. Konda, F. Germano, D. Farini, C. Manna, and G. Siracusa Spatiotemporal Patterns of Expression of Neurotrophins and Neurotrophin Receptors in Mice Suggest Functional Roles in Testicular and Epididymal Morphogenesis Biol Reprod, October 1, 1999; 61(4): 1123 - 1132. [Abstract] [Full Text]

				S. B. Wade, P. Oommen, W. C. Conner, D. J. Earnest, and R. C. Miranda Overlapping and Divergent Actions of Estrogen and the Neurotrophins on Cell Fate and p53-Dependent Signal Transduction in Conditionally Immortalized Cerebral Cortical Neuroblasts J. Neurosci., August 15, 1999; 19(16): 6994 - 7006. [Abstract] [Full Text] [PDF]

				R. Kraemer, H. Nguyen, K. L. March, and B. Hempstead NGF Activates Similar Intracellular Signaling Pathways in Vascular Smooth Muscle Cells as PDGF-BB But Elicits Different Biological Responses Arterioscler. Thromb. Vasc. Biol., April 1, 1999; 19(4): 1041 - 1050. [Abstract] [Full Text] [PDF]

				R. Brady, S. I. A. Zaidi, C. Mayer, and D. M. Katz BDNF Is a Target-Derived Survival Factor for Arterial Baroreceptor and Chemoafferent Primary Sensory Neurons J. Neurosci., March 15, 1999; 19(6): 2131 - 2142. [Abstract] [Full Text] [PDF]

				Z. F. Cheema, S. B. Wade, M. Sata, K. Walsh, F. Sohrabji, and R. C. Miranda Fas/Apo [Apoptosis]-1 and Associated Proteins in the Differentiating Cerebral Cortex: Induction of Caspase-Dependent Cell Death and Activation of NF-kappa B J. Neurosci., March 1, 1999; 19(5): 1754 - 1770. [Abstract] [Full Text] [PDF]

				S. Baek and K. L. March Gene Therapy for Restenosis : Getting Nearer the Heart of the Matter Circ. Res., February 23, 1998; 82(3): 295 - 305. [Abstract] [Full Text] [PDF]

				L. Tessarollo, P. Tsoulfas, M. J. Donovan, M. E. Palko, J. Blair-Flynn, B. L. Hempstead, and L. F. Parada Targeted deletion of all isoforms of the trkC gene suggests the use of alternate receptors by its ligand neurotrophin-3 in neuronal development and implicates trkC in normal cardiogenesis PNAS, December 23, 1997; 94(26): 14776 - 14781. [Abstract] [Full Text] [PDF]

				J. O. Hiltunen, U. Arumae, M. Moshnyakov, and M. Saarma Expression of mRNAs for Neurotrophins and Their Receptors in Developing Rat Heart Circ. Res., November 1, 1996; 79(5): 930 - 939. [Abstract] [Full Text]

				K. M. F. Khan, D. J. Falcone, and R. Kraemer Nerve Growth Factor Activation of Erk-1 and Erk-2 Induces Matrix Metalloproteinase-9 Expression in Vascular Smooth Muscle Cells J. Biol. Chem., January 11, 2002; 277(3): 2353 - 2359. [Abstract] [Full Text] [PDF]