title: Local expression of C-type natriuretic peptide markedly suppresses neointimal formation in rat injured arteries through an autocrine/paracrine loop.
abstract: BACKGROUND
  In vivo gene transfer into injured arteries may provide a new means to facilitate molecular understanding of and to treat the intractable fibroproliferative arterial diseases. Selection of an optimal molecule to be transferred will be a key to successful gene therapy in the future. We tested the hypothesis that a secreted multifactorial molecule should act more efficiently through an autocrine/paracrine loop to suppress neointimal formation elicited in injured arteries than a simple growth-inhibiting molecule that might be expressed inside cells.
  
  
  RESULTS
  We constructed an adenoviral vector (AdCACNP) expressing C-type natriuretic peptide (CNP), a secreted stimulator of membrane-bound guanyl cyclase. AdCACNP directs cells to secrete large quantities of biologically active CNP. Serum-stimulated DNA synthesis and cell proliferation were only moderately suppressed in arterial smooth muscle cells infected with AdCACNP in vitro. However, when AdCACNP was applied to balloon-injured rat carotid arteries in vivo, neointimal formation was markedly reduced (90% reduction) in an infection-site-specific manner without an increase in plasma CNP level.
  
  
  CONCLUSIONS
  Our results showed that CNP, a secreted multifactorial molecule, was indeed effective in suppressing fibroproliferative response in injured arteries and suggest that the potent antiproliferation effect may not be the most critical factor for the effective suppression of neointimal formation. An adenovirus-mediated expression of CNP could be an effective and site-specific form of molecular intervention in proliferative arterial diseases.
authors.affiliation: Department of Cardiology, Kyushu University School of Medicine, Fukuoka, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Ueno
authors.forename: A
authors.initials: A
authors.lastname: Haruno
authors.forename: N
authors.initials: N
authors.lastname: Morisaki
authors.forename: M
authors.initials: M
authors.lastname: Furuya
authors.forename: K
authors.initials: K
authors.lastname: Kangawa
authors.forename: A
authors.initials: A
authors.lastname: Takeshita
authors.forename: Y
authors.initials: Y
authors.lastname: Saito
mesh_terms: D000256:Adenoviridae; D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology / Q000502:physiology; D009320:Atrial Natriuretic Factor / Q000096:biosynthesis; D002339:Carotid Arteries / Q000502:physiology*; D020212:Carotid Artery Injuries; D002404:Catheterization / Q000009:adverse effects; D002455:Cell Division; D002462:Cell Membrane / Q000201:enzymology; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D006162:Guanylate Cyclase / Q000378:metabolism; D006801:Humans; D020098:Natriuretic Peptide, C-Type; D014176:Protein Biosynthesis; D011506:Proteins / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000096:biosynthesis; D013552:Swine; D017539:Tunica Intima / Q000166:cytology / Q000293:injuries* / Q000502:physiology*
chemical_list: D011506:Proteins; D011994:Recombinant Proteins; D020098:Natriuretic Peptide, C-Type; D009320:Atrial Natriuretic Factor; D004247:DNA; D006162:Guanylate Cyclase