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Stress alters vascular–endothelial growth factor expression in rat arteries: Role of nerve growth factor

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Abstract

The aim of this study was to investigate the role of stress and nerve growth factor (NGF) on the expression of vascular–endothelial growth factor (VEGF) and NGF high–affinity receptor (tyrosine kinase A, TrKA) in the ascending and abdominal aorta.

Adult male rats were exposed to immobilization stress for one hour or injected with purified murine NGF. Four hours after treatments, rats were sacrificed and VEGF, NGF and TrkA expression in ascending and abdominal aorta evaluated. The effects of anti–NGF treatment on arterial VEGF expression and on stress–induced arterial cell proliferation were also studied in control and stressed rats.

The data indicated that both stress and NGF injection induced a rapid increase of arterial VEGF associated with an elevated level of NGF and TrkA in arterial tissues. Blocking NGF action by neutralizing NGF–antibodies, results in down–regulation of stress–induced VEGF expression by arteries and in the blockade of stress–induced proliferation of cells from the arterial wall.

Overall our data demonstrated that NGF is involved in the regulation of VEGF and in cardiac vessels response after emotional stress.

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References

  1. Abe T, Morgan DA, Gutterman DD (1997) Protective role of nerve growth factor against postischemic dysfunction of sympathetic coronary innervation. Circulation 95:213–220

    CAS  PubMed  Google Scholar 

  2. Aloe L, Bracci-Laudiero L, Alleva E, Lambiase A, Micera A, Tirassa P (1994) Emotional stress induced by parachute jumping enhances blood nerve growth factor levels and the distribution of nerve growth factor receptors in lymphocytes. Proc Natl Acad Sci USA 91:10440–10444

    Google Scholar 

  3. Aloe L, Tirassa P, Bracci-Laudiero L (2001) Nerve growth factor in neurological and non-neurological diseases: basic .ndings and emerging pharmacological prospectives. Curr Pharm Des 7:113–123

    Google Scholar 

  4. Bersani G, Iannitelli A, Fiore M, Angelucci F, Aloe L (2000) Data and hypotheses on the role of nerve growth factor and other neurotrophins in psychiatric disorders. Med Hypotheses 55:199–207

    Google Scholar 

  5. Bocchini V, Angeletti PU (1969) The nerve growth factor: purification as a 30,000-molecular-weight protein. Proc Natl Acad Sci USA 64:787–794

    Google Scholar 

  6. Callahan MF, da Rocha MJ, Morris M (1992) Sinoaortic denervation does not increase cardiovascular/endocrine responses to stress. Neuroendocrinology 56:735–744

    Google Scholar 

  7. Calza L, Giardino L, Giuliani A, Aloe L, Levi-Montalcini R (2001) Nerve growth factor control of neuronal expression of angiogenetic and vasoactive factors. Proc Natl Acad Sci USA 98:4160–4165

    Google Scholar 

  8. Cantarella G, Lempereur L, Presta M, Ribatti D, Lombardo G, Lazarovici P, Zappala G, Pafumi C, Bernardini R (2002) Nerve growth factor-endothelial cell interaction leads to angiogenesis in vitro and in vivo. Faseb J 16:1307–1309

    Google Scholar 

  9. Cao JM, Chen LS, KenKnight BH, Ohara T, Lee MH, Tsai J, Lai WW, Karagueuzian HS, Wolf PL, Fishbein MC, Chen PS (2000) Nerve sprouting and sudden cardiac death. Circ Res 86:816–821

    CAS  PubMed  Google Scholar 

  10. Carlier PG, Crine AF, Yerna NM, Rorive GL (1988) Cardiovascular structural changes induced by isolation-stress hypertension in the rat. J Hypertens Suppl 6:S112–115

    Google Scholar 

  11. Chaldakov GN, Fiore M, Hristova MG, Aloe L (2003) Metabotrophic potential of neurotrophins:implication in obesity and related diseases? Med Sci Monit 9:HY19–HY21

    Google Scholar 

  12. Chaldakov GN, Fiore M, Stankulov IS, Hristova M, Antonelli A, Manni L, Ghenev PI, Angelucci F, Aloe L (2001) NGF, BDNF, leptin, and mast cells in human coronary atherosclerosis and metabolic syndrome. Arch Physiol Biochem 109:357–360

    Google Scholar 

  13. Chiaretti A, Piastra M, Caresta E, Nanni L, Aloe L (2002) Improving ischaemic skin revascularisation by nerve growth factor in a child with crush syndrome. Arch Dis Child 87:446–448

    Google Scholar 

  14. Dor Y, Djonov V, Keshet E (2003) Induction of vascular networks in adult organs: implications to proangiogenic therapy. Ann N Y Acad Sci 995:208–216

    Google Scholar 

  15. Emanueli C, Salis MB, Pinna A, Graiani G, Manni L, Madeddu P (2002) Nerve growth factor promotes angiogenesis and arteriogenesis in ischemic hindlimbs. Circulation 106:2257–2262

    Google Scholar 

  16. Ferrara N, Gerber HP, LeCouter J (2003) The biology of VEGF and its receptors. Nat Med 9:669–676

    Article  CAS  PubMed  Google Scholar 

  17. Foreman PJ, Taglialatela G, Angelucci L, Turner CP, Perez-Polo JR (1993) Nerve growth factor and p75NGFR factor receptor mRNA change in rodent CNS following stress activation of the hypothalamopituitary-adrenocortical axis. J Neurosci Res 36:10–18

    Google Scholar 

  18. Graiani G, Emanueli C, Desortes E, Van Linthout S, Pinna A, Figueroa CD, Manni L, Madeddu P (2004) Nerve growth factor promotes reparative angiogenesis and inhibits endothelial apoptosis in cutaneous wounds of Type 1 diabetic mice. Diabetologia 47:1047–1054

    Google Scholar 

  19. Hassankhani A, Steinhelper ME, Soonpaa MH, Katz EB, Taylor DA, Andrade- Rozental A, Factor SM, Steinberg JJ, Field LJ, Federoff HJ (1995) Overexpression of NGF within the heart of transgenic mice causes hyperinnervation, cardiac enlargement, and hyperplasia of ectopic cells. Dev Biol 169:309–321

    Google Scholar 

  20. Heath BM, Xia J, Dong E, An RH, Brooks A, Liang C, Federoff HJ, Kass RS (1998) Overexpression of nerve growth factor in the heart alters ion channel activity and beta-adrenergic signalling in an adult transgenic mouse. J Physiol 512 (Pt 3):779–791

    Google Scholar 

  21. Herd JA (1991) Cardiovascular response to stress. Physiol Rev 71:305–330

    Google Scholar 

  22. Hiltunen JO, Laurikainen A, Vakeva A, Meri S, Saarma M (2001) Nerve growth factor and brain-derived neurotrophic factor mRNAs are regulated in distinct cell populations of rat heart after ischaemia and reperfusion. J Pathol 194:247–253

    Google Scholar 

  23. Kaye DM, Vaddadi G, Gruskin SL, Du XJ, Esler MD (2000) Reduced myocardial nerve growth factor expression in human and experimental heart failure. Circ Res 86:E80–E84

    Google Scholar 

  24. Kuwahara F, Kai H, Tokuda K, Shibata R, Kusaba K, Tahara N, Niiyama H, Nagata T, Imaizumi T (2002) Hypoxia-inducible factor-1alpha/vascular endothelial growth factor pathway for adventitial vasa vasorum formation in hypertensive rat aorta. Hypertension 39:46–50

    Google Scholar 

  25. Levi-Montalcini R (1987) The nerve growth factor 35 years later. Science 237:1154–1162

    CAS  PubMed  Google Scholar 

  26. Lockhart ST, Turrigiano GG, Birren SJ (1997 Dec 15) Nerve growth factor modulates synaptic transmission between sympathetic neurons and cardiac myocytes. J Neurosci 17:9573–9582

    Google Scholar 

  27. Middeke M, Hoffmann S, Hassan I, Wunderlich A, Hofbauer LC, Zielke A (2002) In vitro and in vivo angiogenesis in PC12 pheochromocytoma cells is mediated by vascular endothelial growth factor. Exp Clin Endocrinol Diabetes 110:386–392

    Google Scholar 

  28. Onuki Y, Kouchi Y, Yoshida H, Wu MH, Shi Q, Wechezak AR, Coan D, Sauvage LR (1998) Early flow surface endothelialization before microvessel ingrowth in accelerated graft healing, with BrdU identification of cellular proliferation. Ann Vasc Surg 12:207–215

    Google Scholar 

  29. Plante GE (2002) Vascular response to stress in health and disease. Metabolism 51:25–30

    Google Scholar 

  30. Qin F, Vulapalli RS, Stevens SY, Liang CS (2002) Loss of cardiac sympathetic neurotransmitters in heart failure and NE infusion is associated with reduced NGF. Am J Physiol Heart Circ Physiol 282:H363–H371

    Google Scholar 

  31. Raychaudhuri SK, Raychaudhuri SP, Weltman H, Farber EM (2001) Effect of nerve growth factor on endothelial cell biology: proliferation and adherence molecule expression on human dermal microvascular endothelial cells. Arch Dermatol Res 293:291–295

    Google Scholar 

  32. Salis MB, Graiani G, Desortes E, Caldwell RB, Madeddu P, Emanueli C (2004) Nerve growth factor supplementation reverses the impairment, induced by Type 1 diabetes, of hindlimb post-ischaemic recovery in mice. Diabetologia 47:1055–1063

    Google Scholar 

  33. Samii A, Unger J, Lange W (1999) Vascular endothelial growth factor expression in peripheral nerves and dorsal root ganglia in diabetic neuropathy in rats. Neurosci Lett 262:159–162

    Google Scholar 

  34. Santos PM, Winterowd JG, Allen GG, Bothwell MA, Rubel EW (1991) Nerve growth factor: increased angiogenesis without improved nerve regeneration. Otolaryngol Head Neck Surg 105:12–25

    Google Scholar 

  35. Tanaka A, Wakita U, Kambe N, Iwasaki T, Matsuda H (2004) An autocrine function of nerve growth factor for cell cycle regulation of vascular endothelial cells. Biochem Biophys Res Commun 313:1009–1014

    Google Scholar 

  36. Tirassa P, Manni L, Stenfors C, Lundeberg T, Aloe L (2000) RT-PCR ELISA method for the analysis of neurotrophin mRNA expression in brain and peripheral tissues. J Biotechnol 84:259–272

    Google Scholar 

  37. Turrini P, Gaetano C, Antonelli A, Capogrossi MC, Aloe L (2002) Nerve growth factor induces angiogenic activity in a mouse model of hindlimb ischemia. Neurosci Lett 323:109–112

    Google Scholar 

  38. Tuveri M, Generini S, Matucci-Cerinic M, Aloe L (2000) NGF, a useful tool in the treatment of chronic vasculitic ulcers in rheumatoid arthritis. Lancet 356:1739–1740

    Google Scholar 

  39. Wu W, Murata J, Murakami K, Yamaura T, Hayashi K, Saiki I (2000) Social isolation stress augments angiogenesis induced by colon 26-L5 carcinoma cells in mice. Clin Exp Metastasis 18:1–10

    Google Scholar 

  40. Xu C, Lee S, Singh TM, Sho E, Li X, Sho M, Masuda H, Zarins CK (2001) Molecular mechanisms of aortic wall remodeling in response to hypertension. J Vasc Surg 33:570–578

    Google Scholar 

  41. Xu Q, Li DG, Holbrook NJ, Udelsman R (1995) Acute hypertension induces heatshock protein 70 gene expression in rat aorta. Circulation 92:1223–1229

    Google Scholar 

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Authors and Affiliations

  1. Institute of Neurobiology and Molecular Medicine, Section of Neurobiology, CNR, Viale Marx, 43/15, 00137, Roma, Italy

    L. Manni, A. Antonelli &  L. Aloe

  2. Università degli Studi “Magna Grecia”, Catanzaro, Italy

    N. Costa

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  1. L. Manni
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  2. A. Antonelli
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  3. N. Costa
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  4. L. Aloe
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Correspondence to L. Aloe.

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Manni, L., Antonelli, A., Costa, N. et al. Stress alters vascular–endothelial growth factor expression in rat arteries: Role of nerve growth factor. Basic Res Cardiol 100, 121–130 (2005). https://doi.org/10.1007/s00395-004-0502-7

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  • DOI: https://doi.org/10.1007/s00395-004-0502-7

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