Systemic tissue inhibitor of metalloproteinase-1 gene delivery reduces neointimal hyperplasia in balloon-injured rat carotid artery.
Metalloproteinases (MMP)-2 and MMP-9 play a role in smooth muscle cell (SMC) migration from the media to the intima following arterial injury. Intravenous administration of adenovirus encoding tissue inhibitor of metalloproteinase-1 (TIMP-1) into balloon-injured rat arteries (3 x 10(11) viral particles/rat; n=7) resulted in a transient expression of TIMP-1 and a significant inhibition of neointima thickening within 16 days ( approximately 40% vs. control; P=0.012). Three days after injury, the number of intimal SMCs was decreased by approximately 98% in TIMP-1-treated rats. However, no alteration was seen in intimal SMC proliferation after 13 days of injury. Therefore, our results show that systemic gene transfer of TIMP-1 is a promising approach in early restenosis treatment.
Furman
C
C
Institut Pasteur de Lille and INSERM U-545, 1, rue du Professeur Calmette, Lille, France.
Luo
Z
Z
Walsh
K
K
Duverger
N
N
Copin
C
C
Fruchart
J C
JC
Rouis
M
M
D000256:Adenoviridae / Q000235:genetics; D000800:Angioplasty, Balloon / Q000009:adverse effects*; D000818:Animals; D002339:Carotid Arteries / Q000473:pathology*; D016893:Carotid Stenosis / Q000209:etiology / Q000473:pathology / Q000628:therapy*; D002465:Cell Movement; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000008:administration & dosage; D006801:Humans; D006965:Hyperplasia; D007275:Injections, Intravenous; D007700:Kinetics; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood / Q000235:genetics*
D019715:Tissue Inhibitor of Metalloproteinase-1; D020782:Matrix Metalloproteinases