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Elimination of vascular fibrointimal hyperplasia bysomatostatin receptor 1.4 selective agonist
Author(s) -
Aavik Einari,
Luoto NinaMaria,
Petrov Lubomir,
Aavik Silja,
Patel Yogesh C.,
Hayry Pekka
Publication year - 2002
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.01-0272fje
Subject(s) - restenosis , octreotide , somatostatin , somatostatin receptor , intimal hyperplasia , medicine , receptor , agonist , progenitor cell , neointimal hyperplasia , endocrinology , hyperplasia , in vitro , chemistry , biology , stent , smooth muscle , stem cell , microbiology and biotechnology , biochemistry
The somatostatin analogs octreotide and lanreotide, selective to receptor subtypes 2 and 5, failed clinical efficacy for the prevention of restenosis after percutaneous transluminal angioplasty. These findings might have been the result of targeting a wrong subset of receptors. In rat arteries, subtypes 1 and 4 are expressed 3–4 times more prominently than 2 and 5, and subtype 1 is the nearly exclusive subtype in atherosclerotic human vessels. Here, we demonstrate that daily s.c. injections (50–500µg/kg/d) of CH275 (DesAA1,2,5(D‐W8,IAmp9)Somatostatine‐14), selective to subtypes 1 and 4, dose‐dependently inhibited intimal hyperplasia 14 days after rat carotid denudation injury (for intimal area P =0.0002 across the dose range). CH275 was more effective than somatostatin‐14 (equal affinity to all five subtypes, P =0.03), or octreotide (selective to subtypes 2 and 5, P =0.098). When rats were given the peptides for 14 days with end‐point at 28 days, CH275 still significantly inhibited intimal area expansion. Both CH275 and octreotide inhibited the outgrowth of cells from postinjury aortic tissue punch‐explants and the distance migrated in vitro, but not cell replication, which indicated that the effects of somatostatin analogs were directed on the migration of intimal cell progenitors rather than on their proliferation.