DESCRIZIONE E ANALISI DEI RISULTAT
22 Identificazione delle proteine tramite spettrometria di massa
Gli spots elettroforetici, visualizzati con la colorazione “blue Silver” ottenuta mediante Coomassie G-250 colloidale, vengono ritagliati manualmente con molte precauzioni per evitare contaminazioni. Gli spot vengono quindi decolorati, secondo il metodo descritto da Shevchenko ed al. (1996), con una soluzione 1:1 di Acetonitrile e NH4HCO3 50 mM, quindi disidratati con lavaggi in Acetonitrile. Successivamente, si aggiunge una soluzione di Tripsina 5 ng/μl in NH4HCO3 25 mM. La digestione proteolitica della proteina nel gel a dare frammenti peptidici viene condotta a 37 °C per tutta la notte. Il digerito triptico (0.75 μL/spot) viene diluito 1:1 con una soluzione satura di matrice CHCA in 50% acetonitrile e 0,1% v/v TFA e applicato sulla piastra dello spettrometro MALDI TOF (0,3 µl di soluzione per pozzetto). La quantità deposta sulla piastra lasciata asciugare lentamente all’aria. L’impronta digitale dello spettro di massa dei frammenti petidici, “Peptide Mass Fingerprinting”, viene acquisita utilizzando uno spettrometro di massa OmniFLEX MALDI-TOF mass spectrometer (Bruker Daltonics Corporation, Billerica MA, USA). Il profilo del digerito triptico ottenuto viene confrontato con quelli delle proteine note presenti nelle banche di dati utilizzando
programmi disponibili in rete quali: ProFound
93
(http://129.85.19.192/profound_bin/WebProFound.exe), PeptIdent (http://www.expasy.org),
MASCOT (Matrix Science, London, UK; http://www.matrixscience.com). Se il “Peptide mass fingerprinting” della proteina da identificare corrisponde a quello riportato in una banca dati si ottiene l’identificazione della proteina.
94 CONCLUSIONI
95 23 Conclusioni
La comprensione dei meccanismi molecolari che regolano la modulazione fenotipica delle VSMC è una tematica di grande importanza in quanto questo fenomeno è associato con la maggior parte delle patologie cardiovascolari. Scopo di questo lavoro è stato lo studio a livello proteico dei cambiamento precoci in grado di innescare le cascate di segnali che portano all’acquisizione di un nuovo fenotipo. A questo scopo ho analizzato le elettroforesi bidimensionali di VSMC in stato quiesciente e le ho confrontate con quelle di cellule attivate per 48h con siero. Alcune delle proteine che presentavano una espressione differenziale sono state identificate e sequenziate tramite spettrometria di massa. La modulazione in tirosin- fosforilazione di queste proteine è stata monitorata a tempi diversi dalla stimolazione con siero o con singoli fattori di crescita (IGF-1 e PDGF-BB).
In sintesi ho potuto documentare un iniziale generale decremento in tirosin- fosforilazione nei primi minuti successivi la stimolazione. Questa osservazione è interessante e suggerisce un possibile ruolo di fosfatasi nell’avviare il processo di attivazione in stadi precoci. I dati da me ottenuti sono descrittivi e preliminari, ma nuovi e originali e meritano di essere ulteriormente investigati.
La principale caratteristica che si presenta negli stadi prococi dell’attivazione è il reclutamento di chaperonine, molecole che sono implicate nel ‘maquillage’ e riciclo di proteine pre-esistenti all’interno della cellula. La maggior parte di queste proteine agisce sul rimodellamento citoschletrico e molte sono correlate con la migrazione cellulare.
Tale evidenza è in accordo con recenti ipotesi che propongono l’aterogenesi come una patologia prodotta dall’accumulo di proteine “misfolded” citotossiche e pro-infiammatorie. (Ursini et al. 2002)
96 RIFERIMENTI BIBLIOGRAFICI
Abedi, H., Zachary, I. (1995) Signalling mechanisms in the regulation of vascular cell migration. Cardiovasc. Res. 30, 544–556.
Anderson and Subodh Verma Paul E. Szmitko, Chao-Hung Wang, Richard D. Weisel, John R. De Almeida, Todd J.(2003) New Markers of Inflammation and Endothelial Cell Activation: Part I Circulation ;108;1917-1923
Angela M. Taylor and Coleen A. McNamara (2003) Common Pathway Regulation of Vascular Smooth Muscle Cell Growth: Targeting the Final Arterioscler. Thromb. Vasc. Biol. ;23;1717-1720
B.G. Katzung (2000) “Farmacologia generale e clinica” Piccin
Barazi HO, Zhou L, Templeton NS, Krutzsch HC, Roberts DD (2002) Identification of heat shock protein 60 as a molecular mediator ofα3β1 integrin activation. Cancer Res 62:1541–1548
Barrett TB, Benditt EP. (1987) Sis(platelet-derived growth factor B chain) gene transcript levels are elevated in human atherosclerotic lesions compared to normal artery. Proc Natl Acad Sci USA ;84:1099–103.
Barrett TB, Benditt EP. (1988) Platelet-derived growth factor gene expression in human atherosclerotic plaques and normal artery wall. Proc Natl Acad Sci USA ;85(8):2810–4. Barrett TB, Benditt EP. (1988) Platelet-derived growth factor gene expression in human
atherosclerotic plaques and normal artery wall. Proc Natl Acad Sci USA ;85(8):2810–4. Barrett TB, Seifert RA, Bowen-Pope DF. (1996) Regulation of platelet-derived growth factor
receptor expression by cell context overrides regulation by cytokines. J Cell Physiol.; 169:126–38.
Bennett M.R. (2003) in-stent stenosis: pathology and implications for the development of drug eluting stents Heart ;89:218–224
Bergers G, Song S, Meyer-Morse N, Bergsland E, Hanahan D. (2003) Benefits of targeting both pericytes and endothelial cells in the tumor vasculature with kinase inhibitors. J Clin Invest.; 111: 1287–95.
Björkerud S and Björkerud B. (1997) Is abundant in human atherosclerotic lesions, especially in inflammatory cells (macrophages and T cells) and may contribute to the accumulation of gruel and plaque instability. Am J Pathol 149: 367-80.
Boccardi C, Cecchettini A, Caselli A Camici G, Evangelista M, Mercatanti A, Rainaldi G, Citti L (2006) A proteomic approach to the investigation of early events involved in vascular smooth muscle cell activation Cell Tissue Res
Campbell GR, Campbell JH (1985) Smooth muscle phenotypic changes in arterial wall homeostasis: implications for pathogenesis of atherosclerosis. Exp Mol Path 42: 139–62 Campbell GR, Campbell JH, Manderson JA, Horrigan S, Rennick RE (1988) Arterial smooth
muscle. A multifunctional mesenchymal cell. Arch Pathol Lab Med. Oct;112(10):977- 86
Casscells W. (1991) Smooth muscle cell growth factors. Progr Growth Factor Res 3: 177- 206.
Catherine M. Shanahan and Peter L. Weissberg (1998) Smooth Muscle Cells In Vitro and In
97 Vivo Smooth Muscle Cell Heterogeneity : Patterns of Gene Expression in Vascular Thromb. Vasc. Biol.;18;333-338
Cecka J and Terasaski P. (1993) The Unos scientific renal transplant registry. Los Angeles, Terasaki and Cecka
Cercek B, Fishbein MC, Forrester J, Helfant R and Fagin J. (1990) Induction of insulin-like growth factor 1 messenger RNA in rat aorta after balloon denudation. Circ Res 66: 1755-1760.
Cercek B, Sharifi B, Barath P, Bailey L and Forrester J. (1991) Growth factors in the pathogenesis of coronary arterial restenosis. Am J Cardiol63: 24C-33C.
Che W, Lerner-Marmarosh N, Huang Q, Osawa M, Ohta S, Yoshizumi M, Glassman M, Lee JD, Yan C, Berk BC, Abe J. (2002) Insulin-like growth factor-1 enhances inflammatory responses in endothelial cells: role of Gab1 and MEKK3 in TNF-a´-induced c-Jun and NF-_B activation and adhesion molecule expression. Circ Res. ;90:1222–1230.
Chen TG, Chen JZ, Wang XX (2006) Effects of rapamycin on number activity and eNOS of endothelial progenitor cells from peripheral blood Cell Prolif. Apr;39(2):117-25
Chiarugi P, Cirri P, Taddei ML, Talini D, Doria L, Fiaschi T, Buricchi F, Giannoni E, Camici G, Raugei G, Ramponi G. (2002) New perspectives in PDGF receptor downregulation: the main role of phosphotyrosine phosphatases. J Cell Sci.; 115: 2219–32.
Christen T, Verin V., Bochaton-Piallat ML, Popowski Y., Ramaekers F.,Debruyne P., Camenzind E., van Eys G., PhD; Gabbiani G, (2001) Mechanisms of Neointima Formation and Remodeling in the Porcine Coronary Artery Circulation. ;103:882
Citti L., Rainaldi G. (2005) Synthetic hammerhead ribozymes as therapeutic tools to control disease genes” Current Gene Therapy 5, 11-24
Clemmons DR, Horvitz G, Engleman W, Nichols T, Moralez A, Nickols GA. (1999) Synthetic a´Vaˆ3 antagonists inhibit insulin-like growth factor-Istimulated smooth muscle cell migration and replication. Endocrinology.;140:4616–4621.
Cohick WS, Gockerman A, Clemmons DR. (1993) Smooth muscle cells synthesize two forms of insulin-like growth factor binding proteins which are regulated differently by the insulin-like growth factors. J Cell Physiol. ;157:52–60.
Crowley ST, Ray CJ, Nawaz D, Majack RA and Horwitz LD. (1995) Multiple growth factors are released from mechanically injured vascular smooth muscle cells. Am J Physiol 269:H1641-H1647.
Delafontaine P , Song YA and Li Y (2004) Expression, Regulation, and Function of IGF-1, IGF-1R, and IGF-1 Binding Proteins in Blood Vessels Arterioscler. Thromb. Vasc. Biol. ;24;435-444;
Delafontaine P, Lou H, Alexander RW. (1991) Regulation of insulin-like growth factor I messenger RNA levels in vascular smooth muscle cells. Hypertension. ;18:742–747. Delafontaine P. (1995) Insulin-like growth factor I and its binding proteins in the
cardiovascular system. Cardiovasc Res. 1995;30:825–834.
Diez J. (1999) Insulin-like growth factor I in essential hypertension. Kidney Int. ;55:744–759. Du J, Sperling LS, Marrero MB, Phillips L, Delafontaine P. (1996) G-protein and tyrosine
kinase receptor cross-talk in rat aortic smooth muscle cells: thrombin- and angiotensin II-induced tyrosine phosphorylation of insulin receptor substrate-1 and insulin-like growth factor 1 receptor. Biochem Biophys Res Commun. ;218:934–939.
Duan C, Hawes SB, Prevette T, Clemmons DR. (1996) Insulin-like growth factor-I (IGF-I) regulates IGF-binding protein-5 synthesis through transcriptional activation of the gene
98 in aortic smooth muscle cells. J Biol Chem. ;271:4280–4288.
Enge M, Bjarnegard M, Gerhardt H, Gustafsson E, Kalen M, Asker N, et al. (2002) Endothelium-specific platelet-derived growth factor-B ablation mimics diabetic retinopathy. EMBO J ;21:4307–16.
Eriksson A, Siegbahn B, CH Westermark, c.-h. Heldin, and l. Claesson-Welsh. (1992) PDGF a- and b-receptors activate unique and common signal transduction pathways. EMBO J. 11:543–550
Evanko SP, Raines EW, Ross R, Gold LI, Wight TN. (1998) Proteoglycan distribution in lesions of atherosclerosis depends on lesion severity, structural characteristics, and the proximity of platelet-derived growth factor and transforming growth factor-beta. Am J Pathol 1998;152(2):533–46.
Fath KA, Alexander RW, Delafontaine P. (1993) Abdominal coarctation increases insulin-like growth factor I mRNA levels in rat aorta. Circ Res. ;72:271–277.
Ferns GAA, Raines EW, Sprugel KH, Motani AS, Reidy MA and Ross R. (1991) Inhibition of neointimal smooth muscle accumulation after angioplasty by an antibody to PDGF. Science 253: 1129-1132.
Floege J, Hudkins KL, Davis CL, Schwartz SM, Alpers CE. (1998) Expression of PDGF alpha-receptor in renal arteriosclerosis and rejecting renal transplants. J Am Soc Nephrol ;9(2):211–23.
Fuster V., Alexander R.W., O’Rourke R.A., Roberts R., King S.B., Nash I.S., Prystowsky E.N. (2005) “Il cuore” 11° Edizione McGrow-Hill
Gallo R, Padurean A, Jayaraman T, Marx S, Roque M, Adelman S, Chesebro J, Fallon J, , Marks A, Badimon JJ. (1999) Inhibition of intimal thickening after balloon angioplasty in porcine coronary arteries by targeting regulators of the cell cycle. Circulation. ;99(16):2164-70
Gary K. Owens, Meena S. Kumar and Brian R. Wamhoff (2004) Molecular Regulation of Vascular Smooth Muscle Cell Differentiation in Development and Disease Physiol. Rev. 84: 767-801
Gilbertson DG, Duff ME, West JW, Kelly JD, Sheppard PO, Hofstrand PD, et al. (2001) Platelet-derived growth factor C (PDGF-C), a novel growth factor that binds to PDGF alpha and beta receptor. J Biol Chem ;276(29):27406–14.
Gordon D. (1992) Growth factors and cell proliferation in human transplant arteriosclerosis. J Heart Lung Transpl 11: 57.
Grant MB, Wargovich TJ, Ellis EA, Tarnuzzer R, Caballero S, Estes K, Rossing M, Spoerri PE, Pepine C. (1996) Expression of IGF-I, IGF-I receptor and IGF binding proteins-1, - 2, -3, -4 and -5 in human atherectomy specimens. Regul Pept. ;67:137–144.
Gruentzig AR, King SB, Schlumph M and Siegenthaler W. (1987) Long-term follow-up after percutaneous transluminal angioplasty: The early Zürich experience. N Engl J Med 316:1127-1132.
Hao H, Ropraz P, Verin V, Camenzind E, Geinoz A, Pepper MS, Gabbiani G, and Bochaton- Piallat ML. (2002) Heterogeneity of smooth muscle cell populations cultured from pig coronary artery. Arterioscler Thromb Vasc Biol 22: 1093–1099,
Harjot K. Saini a, Yan-Jun Xu a, Amarjit S. Arneja b, Paramjit S. Tappia c, Naranjan S. Dhalla (2005) Pharmacological basis of different targets for the treatment of atherosclerosis J. Cell. Mol. Med. Vol 9, No 4, pp. 818-839
Harry C. Lowe, FRACP, PHD, Stephen N. Oesterle, MD, FACC,Levon M. Khachigian (2002) Coronary In-Stent Restenosis:Current Status and Future Strategies J Am Coll
99 Cardiol. Jan 16;39(2):183-93
Hayashi K, Shibata K, Morita T, Iwasaki K, Watanabe M, Sobue K (2004) Insulin receptor substrate-1/SHP-2 interaction, a phenotype-dependent switching machinery of insulin- like growth factor-I signaling in vascular smooth muscle cells. J Biol Chem 279:40807– 40818
Hayashi K, Shibata K, Morita T, Iwasaki K, Watanabe M, Sobue K (2004) Insulin receptor substrate-1/SHP-2 interaction, a phenotype-dependent switching machinery of insulin- like growth factor-I signaling in vascular smooth muscle cells. J Biol Chem 279:40807– 40818
Heald AH, Siddals KW, Fraser W, Taylor W, Kaushal K, Morris J, Young RJ, White A, Gibson JM. (2002) Low circulating levels of insulin-like growth factor binding protein- 1 (IGFBP-1) are closely associated with the presence of macrovascular disease and hypertension in type 2 diabetes. Diabetes. ;51:2629–2636.
Heldin CH and Westermark B. (1999) Mechanism of Action and In Vivo Role of Platelet- Derived Growth Factor PHYSIOLOGICAL REVIEWS Vol. 79, No. 4, October 1999 Heldin CH, Westermark B, Wasteson A. (1981) Platelet-derived growth factor. Isolation by a
large-scale procedure and analysis of subunit composition. Biochem J ;193(3):907–13. Heldin CH, Westermark B. (1999) Mechanism of action and in vivo role of platelet-derived
growth factor. Physiol Rev ;79(4):1283–316.
Hellstrom M, Kalen M, Lindahl P, Abramsson A, Betsholtz C. (1999) Role of PDGF-B and PDGFR-beta in recruitment of vascular smooth muscle cells and pericytes during embryonic blood vessel formation in the mouse. Development.; 126: 3047–55.
Hermsmeyer K. (1993) Calcium channel function in hypertension J Hum Hypertens 7: 173– 176
Hogg PJ, Hotchkiss KA, Jimenez BM, Stathakis P, Chesterman CN (1997) Interaction of platelet-derived growth factor with thrombospondin 1. Biochem J 326:709–716
Holmes D, Vliestra R, Smith H, Vetrovec G, Kent K, Cowley M and Mock M. (1984) Restenosis after percutaneous translumnal coronary angioplasty. Am J Cardiol 53: 77C- 81C.
Johansson, B., Eriksson, A., Ramaekers, F., Thornell, L.E. (1999) Smoothelin and intermediate filament proteins in human aortocoronary saphenous vein by-pass grafts. Histochem. J. 31, 723–727.
Jones JI, Clemmons DR. (1995) Insulin-like growth factors and their binding proteins: biological actions. Endocr Rev. ;16:3–34.
Jones JI, Gockerman A, Busby WH Jr, Wright G, Clemmons DR. (1993) Insulin-like growth factor binding protein 1 stimulates cell migration and binds to the a´5aˆ1 integrin by means of its Arg-Gly-Asp sequence. Proc Natl Acad Sci U S A. ;90:10553–10557. Juul A, Scheike T, Davidsen M, Gyllenborg J, Jorgensen T. (2002) Low serum insulin-like
growth factor I is associated with increased risk of ischemic heart disease: a population- based case-control study. Circulation. ; 106:939–944.
Kanzaki T, Tamura K, Takahashi K, Saito Y, Akikusa B, Oohashi H, Kasayuki N, Ueda M and Morisaki N. (1995) In vivo effect of TGF-ß1. Arterioscler Thromb Vasc Biol 15: 1951- 1957.
Keiji Sakai, Walker H. Busby, Jr., Jane B. Clarke, and David R. Clemmons (2001) Tissue Transglutaminase Facilitates the Polymerization of Insulin-like Growth Factor-binding Protein-1 (IGFBP-1) and Leads to Loss of IGFBP-1’s Ability to Inhibit Insulin-like
100 Growth Factor-I-stimulated Protein Synthesis Biol. Chem., Vol. 276, Issue 12, 8740- 8745,
Kelman, Z. (1997) PCNA: structure, functions and interactions. Oncogene 14, 629–640. LaRochelle WJ, Jeffers M, McDonald WF, Chillakuru RA, Giese NA, Lokker NA, et al.
(2001) PDGF-D, a new protease-activated growth factor. Nat Cell Biol ;3(5):517–21. Le Roith D. (1997) Seminars in medicine of the Beth Israel Deaconess Medical Center.
Insulin-like growth factors. N Engl J Med. ;336:633–640.
Lerman A and Eeckhout E. (2006) 126 Coronary endothelial dysfunction following sirolimus-eluting stent placement: should we worry about it? European Heart Journal 27, 125–126
LeRoith D, Werner H, Beitner-Johnson D, Roberts CT Jr. (1995) Molecular and cellular aspects of the insulin-like growth factor I receptor. Endocr Rev. ;16:143–163.
Libby P, Aikawa M. (2002) Stabilization of atherosclerotic plaques: new mechanisms and clinical targets. Nat Med. ;8:1257–1262.
Libby P, Schwartz D, Brogi E, Tanaka H, Clinton SK, (1992) A cascade model for restenosis. Circulation 86: suppl III: 47-52.
Libby P., Ridker PM.,and Maseri A. (2002) Inflammation and Atherosclerosis Circulation;105;1135-1143
Lindahl P, Johansson BR, Leveen P, Betsholtz C. (1997) Pericyte loss and microaneurysm formation in PDGF-B-deficient mice. Science.; 277: 242–5.
Lindner V and Reidy M. (1991) Proliferation of smooth muscle cells after vascular injury is inhibited by an antibody against basic fibroblast growth factor. Proc Natl Acad Sci Liu W, Liu Y, Lowe WL Jr. (2001) The role of phosphatidylinositol 3-kinase and the
mitogen-activated protein kinases in insulin-like growth factor-I-mediated effects in vascular endothelial cells. Endocrinology. ;142:1710–1719.
Majesky MW, Lindner VL, Twardzik DR, Schwartz SM and Reidy MA. (1991) Production of Transforming growth factor ß1 during repair of arterial injury. J Clin Invest 88: 904- 910.
Mayr M., Xu Q.(2001) Smooth muscle cell apoptosis in aterosclerosis Experimental Gerontology 36 969-987
Miano JM, Vlasic N, Tota R and Stemerman M. (1993) Smooth muscle cell immediate-early and growth factor gene activation follows vascular injury: a putative in vivo mechanism for autocrine growth. Arterioscler Thromb 13: 211-219.
Miriuka SG, Rao V, Peterson M, Tumiati L, Delgado DH, Mohan R, Ramzy D, Stewart D, Ross HJ, Waddell TK (2006) mTOR inhibition induces endothelial progenitor cell death. Am J Transplant. Sep;6(9):2069-79.
Nakao-Hayashi J, Ito H, Kanayasu T, Morita I, Murota S (1992) Stimulatory effects of insulin and insulin-like growth factor I on migration and tube formation by vascular endothelial cells. Atherosclerosis. ;92: 141–149.
Nichols TC, Du Laney T, Zheng B, Bellinger DA, Nickols GA, Engleman W, Clemmons DR. (1999) Reduction in atherosclerotic lesion size in pigs by a´Vaˆ3 inhibitors is associated with inhibition of insulin-like growth factor-I-mediated signaling. Circ Res. ;85:1040– 1045.
Patil S.D. Rhodes D.G., Burgess D.J. (2005) Dna based therapeutics and DNA delivery systems: a comprensive review AAPS J. 7, E61-E16.
Patton WF, Erdjument-Bromage H, Marks AR, Tempst P (1995) Components of protein synthesis and folding machinery are induced in vascular smooth muscle cells by
101 hypertrophic and hyperplastic agents. J Biol Chem 270:21404–21410
Perlman H, Luo Z, Krasiniski et al. (1999) Adenoviral-mediated delivery of gax transcription factor to rat carotid arteries inhibits smooth muscle proliferation and induces apoptosis. Gene Ther 6: 758-63.
Pichon S, Bryckaert M, Berrou B (2004) Control of actin dynamics by p38 MAP kinase- Hsp27 distribution in the lamellipodium of smooth muscle cells. J Cell Sci 117:2569– 2577
Pockley AG (2002) Heat shock proteins, inflammation, and cardiovascular disease. Circulation 105:1012–1017
Raines EW, Ross R, editors. (1993) Platelet-derived growth factor in vivo. Basel, Switzerland: Karger
Raines EW, Ross R. (1982) Platelet-derived growth factor. I. High yield purification and evidence for multiple forms. J Biol Chem ;257(9):5154–60.
Rao GN, Delafontaine P, Runge MS. (1995) Thrombin stimulates phosphorylation of insulin- like growth factor-1 receptor, insulin receptor substrate-1, and phospholipase C-a˜1 in rat aortic smooth muscle cells. J Biol Chem. ;270:27871–27875.
Ross R. (1991) Polypeptide growth factors and atherosclerosis. Trends Cardiovasc Med 1: 277-282.
Roy S-G, Nozaki Y, Phan SH (2001) Regulation of alpha-smooth muscle actin gene expression in myofibroblast differentiation from rat lung fibroblasts. Int J Biochem Cell Biol 33:723–734
Rubin K, Tingstrom A, Hansson GK, Larsson E, Ronnstrand L, Klareskog L, et al. (1988) Induction of B-type receptors for plateletderived growth factor in vascular inflammation: possible implications for development of vascular proliferative lesions. Lancet ;1(8599):1353–6.
Saini HK, Arneja AS, Dhalla NS. (2004) Role of cholesterol in cardiovascular dysfunction. Can J Cardiol. ; 20:333–46.
Saltiel AR, Kahn CR. (2001) Insulin signalling and the regulation of glucose and lipid metabolism. Nature. ;414:799–806.
Scheidegger KJ, Cenni B, Picard D, Delafontaine P. (2000) Estradiol decreases IGF-1 and IGF-1 receptor expression in rat aortic smooth muscle cells: mechanisms for its atheroprotective effects. J Biol Chem. ;275:38921–38928.
Scheidegger KJ, Du J, Delafontaine P. (1999) Distinct and common pathways in the regulation of insulin-like growth factor-1 receptor gene expression by angiotensin II and basic fibroblast growth factor. J Biol Chem. ;274:3522–3530.
Schneider MR, Lahm H, Wu M, Hoeflich A, Wolf E. (2000) Transgenic mouse models for studying the functions of insulin-like growth factor-binding proteins. FASEB J. ;14:629–640.
Seifert RA, Hart CE, Phillips PE, Forstrom JW, Ross R, Murray MJ, et al. (1989) Two different subunits associate to create isoform-specific platelet-derived growth factor receptors. J Biol Chem ;264(15):8771–8.
Smith EP, Kamyar A, Niu W, Wang J, Cercek B, Chernausek SD, Fagin JA. (2001) IGF- binding protein-4 expression and IGF-binding protein-4 protease activity are regulated coordinately in smooth muscle during postnatal development and after vascular injury. Endocrinology. ;142:4420–4427.
Smith LE, Shen W, Perruzzi C, Soker S, Kinose F, Xu X, Robinson G, Driver S, Bischoff J, Zhang B, Schaeffer JM, Senger DR. (1999) Regulation of vascular endothelial growth
102 factor-dependent retinal neovascularization by insulin-like growth factor-1 receptor. Nat Med. ;5:1390–1395.
Smith Rc, Branellec D, Gorski DH et al (1997) p21CIP-mediated inhibition of cell proliferation by overexpression of the gax homeodomain gene. Genes Dev 11: 1674-89
Snoeckx LH, Cornelussen RN, Van Nieuwenhoven FA, Reneman RS, Van Der Vusse GJ (2001) Heat shock proteins and cardiovascularpathophysiology. Physiol Rev 81:1461– 1497
Soriano P. (1997) The PDGF alpha receptor is required for neural crest cell development and for normal patterning of the somites. Development.; 124: 2691–700.
Stallone G., Infante B., Schena A., Di Paolo S., Grandaliano G., Gesualdo L., Schena FP. (2004) Il rischio cardiovascolare nel paziente con trapianto renale Giornale Italiano di Nefrologia / Anno 21 n. 2, /pp. 144-155
Tallquist MD, Soriano P. (2003) Cell autonomous requirement for PDGFR alpha in populations of cranial and cardiac neural crest cells. Development.; 130: 507–18.
Terracio L, Rönnstrand L, Tingström A, Rubin K, Claesson-Welsh L, Funa K, Heldin CH. (1988) Induction of platelet-derived growth factor receptor expression in smooth muscle cells and fibroblasts upon tissue culturing. J Cell Biol.; 107: 1947–57.
Thyberg J, Hedin U, Sjölund M, Palmberg L and Bottger BA. (1990) Regulation of differentiated properties and proliferation of arterial smooth muscle cells. Arteriosclerosis 10: 966-990.
Tsuruzoe K, Emkey R, Kriauciunas KM, Ueki K, Kahn CR. (2001) Insulin receptor substrate 3 (IRS-3) and IRS-4 impair IRS-1- and IRS-2-mediated signaling. Mol Cell Biol. ;21:26–38.
Uehara H, Kim SJ, Karashima T, Shepherd DL, Fan D, Tsan R, Killion JJ, Logothetis C, Mathew P, Fidler IJ. (2003) Effects of blocking platelet-derived growth factor-receptor signaling in a mouse model of experimental prostate cancer bone metastases. J Natl Cancer Inst.; 95: 458–70.
Ursini F,.Davies K. J.A, Maiorino M., Parasassi T, Sevanian A. (2002) Atherosclerosis: another protein misfolding disease? TRENDS in Molecular Medicine Vol.8 No.8: 370- 374
Van der Loop FT., Gabbiani G., Kohnen G., Ramaekers FC., van Eys G.J. (1997) Differentiation of smooth muscle cells in human blood vessels as defined by smoothelin, a novel marker for the contractile phenotype. Arterioscler. Thromb. Vasc. Biol. 17, 665– 671.
Vaziri C, Faller DV. (1996) Down-regulation of platelet-derived growth factor receptor expression during terminal differentiation of 3T3-L1 pre-adipocyte fibroblasts. J Biol Chem.; 271: 13642–8.
Walsh K, Perlman H.R., and Smith RC. (1999) Regulation of vascular smooth muscle differentiation and cell cycle. Heart development ;24:429-443
Walsh K., Takahashi A. (2001) Transcriptional regulation of vascular smooth muscle cell phenotype Z Kardiol 90: Suppl 3, III/12 Ð III/16
Wellman GC, Cartin L, Eckman DM, Stevenson AS, Saundry CM, Lederer WJ, and Nelson MT (2001) Membrane depolarization, elevated Ca2 entry, and gene expression in cerebral arteries of hypertensive rats.A m J Physiol Heart Circ Physiol 281: H2559–