Effects of heparinoids on the sclerotic reaction of rat thoracic aorta to injury: comparison between standard and low-molecular-weight heparins in vitro and in vivo.
To assess further the influence of heparinoids on arterial sclerosis, we compared the effects of standard heparin and of a low-molecular-weight (low-mol-wt) heparin (CY 216) in vitro on proliferation of cultured arterial smooth muscle cells (SMC) from rat aorta and in vivo on the sclerotic response of rat thoracic aorta to injury with a balloon catheter (SMC proliferation and deposition of elastin and collagen in the intima-media, using biochemical and histomorphologic techniques). Both heparinoids decreased replication of SMC in vitro in a similar dose-dependent manner. In vivo, heparin treatment [continuous intravenous (i.v.) administration, 60 IU/h/kg body weight (0.35 mg/h/kg)] inhibited all aspects of the aortic reaction for < or = 28 days after injury: synthesis of DNA (early peak of thymidine incorporation into DNA on D3.5); accumulation of DNA, collagen and elastin on D14 and D28; intimal thickening on D14. An equivalent treatment with CY 216 [60 antiactivated factor X (Xa) IU/h/kg (0.71 mg/h/kg)] exerted similar though less intense effects on the reaction of intima-media, as assessed biochemically, but reduced formation of neointima in a proportion nearly identical to that of heparin. In some respects, which appear to be related mainly to the fibrotic reaction of aortic media to injury, heparin tended to be a slightly more potent antisclerotic agent than CY 216 although, owing to pharmacokinetic differences, CY 216 had stronger plasma anti-Xa activity than heparin.
Chajara
A
A
Centre de Recherche sur les Maladies Vasculaires Périphériques, Association Claude Bernard, Paris, France.
Heudes
D
D
Peronneau
I
I
Jarnet
J
J
Basset
A
A
Capron
L
L
D000818:Animals; D001013:Aorta, Thoracic / Q000473:pathology*; D001018:Aortic Diseases / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology*; D002404:Catheterization / Q000009:adverse effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis; D004549:Elastin / Q000378:metabolism; D006493:Heparin / Q000494:pharmacology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D017762:Nadroparin / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012598:Sclerosis; D013917:Thrombin / Q000502:physiology
D017762:Nadroparin; D006493:Heparin; D003094:Collagen; D004247:DNA; D004549:Elastin; D013917:Thrombin