title: Sortilin expression is essential for pro-nerve growth factor-induced apoptosis of rat vascular smooth muscle cells.
abstract: BACKGROUND
  Sortilin, a member of the Vps10p-domain receptor family, has been demonstrated a key regulator in mediating cellular response to pro-neurotrophins. In the present study, we investigated the role of sortilin in the apoptotic pathway of vascular smooth muscle cells.
  
  
  RESULTS
  Immunohistochemistry revealed that sortilin was barely detectable in human and rat normal young vessels, while its expression was increased in human fibroatheromatous plaques. Sortilin immunodetection was also marked in the neointima of the rat aorta fifteen days after ballooning.In vitro, rat aortic intimal cells expressed higher sortilin levels than normal media SMCs; sortilin was distributed in the cytoplasm and in correspondence of the cell membrane. After 48 h, pro-nerve growth factor (proNGF) induced the strong dose-dependent increase of intimal cell apoptosis and the accumulation of sortilin protein. ProNGF was a more potent apoptotic inducer than equimolar or even higher concentration of NGF, whereas brain derived neutrotrophic factor was ineffective. Targeted interfering RNA-mediated sortilin reduction counteracted proNGF-induced apoptosis without affecting p75(NTR) expression. ProNGF-induced apoptosis was associated to NF-κB down-regulation and bax increase. Inhibition of NF-κB activity increased intimal cell apoptosis that did not further increase with the addition of proNGF.
  
  
  CONCLUSIONS
  Our results indicate that sortilin expression characterizes human atheromatous lesions and rat aortic post-injury neointima, and suggest that sortilin represents an important regulator of proNGF-induced SMC apoptosis and arterial remodeling.
authors.affiliation: Department of Biomedicine and Prevention, Anatomic Pathology Institute, University of Rome "Tor Vergata", Rome, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Campagnolo
authors.affiliation: Department of Biomedicine and Prevention, Anatomic Pathology Institute, University of Rome "Tor Vergata", Rome, Italy.
authors.forename: Gaetana
authors.initials: G
authors.lastname: Costanza
authors.affiliation: Department of Biomedicine and Prevention, Anatomic Pathology Institute, University of Rome "Tor Vergata", Rome, Italy.
authors.forename: Arianna
authors.initials: A
authors.lastname: Francesconi
authors.affiliation: Department of Biomedicine and Prevention, Anatomic Pathology Institute, University of Rome "Tor Vergata", Rome, Italy.
authors.forename: Gaetano
authors.initials: G
authors.lastname: Arcuri
authors.affiliation: Department of Biomedicine and Prevention, Anatomic Pathology Institute, University of Rome "Tor Vergata", Rome, Italy ; Department of Molecular Medicine and Gene Therapy, Lund Stem Cell Center, University of Lund, Lund, Sweden.
authors.forename: Ilana
authors.initials: I
authors.lastname: Moscatelli
authors.affiliation: Department of Biomedicine and Prevention, Anatomic Pathology Institute, University of Rome "Tor Vergata", Rome, Italy.
authors.forename: Augusto
authors.initials: A
authors.lastname: Orlandi
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics / Q000378:metabolism*; D000328:Adult; D000367:Age Factors; D000368:Aged; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D002478:Cells, Cultured; D015870:Gene Expression; D020868:Gene Silencing; D006801:Humans; D007150:Immunohistochemistry; D042541:Intracellular Space / Q000378:metabolism; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000378:metabolism*; D020932:Nerve Growth Factor / Q000494:pharmacology*; D021381:Protein Transport; D051381:Rats; D017539:Tunica Intima / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D055815:Young Adult; D000099183:Sortilin
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D020932:Nerve Growth Factor; D000099183:Sortilin