Inhibition of neointimal proliferation in balloon-injured arteries using non-anticoagulant heparin-carrying polystyrene.
Non-anticoagulant heparin-carrying polystyrene (NAC-HCPS) has a higher activity to inhibit proliferation and migration of smooth muscle cells (SMCs) than heparin (Hep), periodate-oxidized (IO4-) Hep, and periodate-oxidized alkaline-degraded low molecular weight (IO4-LMW-) Hep. Less than 10 microg/ml of NAC-HCPS significantly inhibited the proliferation and migration of SMCs in vitro, while over 10-fold higher concentrations of Hep, IO4-Hep, and IO4-LMW-Hep were required to obtain the same inhibition. On the other hand, neointimal growth (intimal cross-section area and intimal cross-section area/medial cross-section area ratio) in vivo following vascular injury 28 days after balloon denudation in a rat carotid artery was substantially inhibited with high dose of intravenous administration (total 30 mg) of respectively IO4-Hep, IO4-LMW-Hep, and NAC-HCPS. A low-dose (total 10 mg) administration of IO4-Hep and IO4-LMW-Hep did not prevent the neointimal growth when compared with the control; only NAC-HCPS (total 10 mg) was able to significantly inhibit the neointimal. Thus, NAC-HCPS has a more-than 10-fold larger activity to inhibit SMC activities such as proliferation and migration in vitro, when comparing with Hep, IO4-Hep, and IO4-LMW-Hep; NAC-HCPS also prevents neointimal growth in vivo at lower doses.
Fujita
Masanori
M
Department of Medical Engineering, Morimoto, National Defense Medical College, Tokorozawa, Saitazma, Japan. BXB01424@nifty.ne.jp
Ishihara
Masayuki
M
Ono
Katsuaki
K
Matsumura
Koji
K
Saito
Yoshio
Y
Yura
Hirofumi
H
Morimoto
Yuji
Y
Shimizu
Masafumi
M
Takase
Bonpei
B
Ozaki
Shigeyuki
S
Kikuchi
Makoto
M
Maehara
Tadaaki
T
D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology*; D002339:Carotid Arteries; D002404:Catheterization / Q000009:adverse effects*; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D005347:Fibroblasts / Q000187:drug effects; D006493:Heparin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D006801:Humans; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000293:injuries* / Q000473:pathology; D011137:Polystyrenes / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D017539:Tunica Intima / Q000187:drug effects*
D000925:Anticoagulants; C461220:NAC-HCPS; D011137:Polystyrenes; D006493:Heparin