Heterogeneity in migration of smooth muscle cells from normal and injured rat thoracic aorta in primary culture.

OBJECTIVE: Aside from proliferation, migration of smooth muscle cells is an essential component of the arterial sclerotic reaction. The aim of this study was to define a model to study migration. METHODS: Primary cultures of smooth muscle cells were derived from normal or injured rat thoracic aorta. An image analysis system was used to track cells migrating out of the explants and measure the displacement of their centre of gravity. RESULTS: Migration speeds for smooth muscle cells randomly sampled from the normal whole media were very heterogeneous. The media were therefore separated into three vertical segments. Cells from the middle third migrated faster than those from the upper and lower thirds, regardless of whether they originated from the anterior and posterior parts of the segment (P = 0.001). Heparin (10 micrograms.ml-1) only inhibited smooth muscle cell migration from the middle segment (P < 0.001). Migration of smooth muscle cells from explants of aorta 3 and 14 d after injury was also studied using a balloon catheter. Three days after injury, cell velocity varied widely among the segments of the same media. In contrast, 14 d after injury cells from neointimal explants migrated homogeneously and at a slower rate than those obtained from normal media. CONCLUSIONS: These experiments show migratory variations among smooth muscle cells depending upon their position in the normal aorta and their state of activation after arterial injury. This variability must be taken into account when planning experiments to study smooth muscle cell migration.

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.