In vivo role of glucocorticoids in barotrauma vascular repair and fibrosis

To determine the important repair events leading to vascular collagen accumulation following barotrauma, in vivo changes were assessed during dexamethasone (DEX) treatment, as well as physiological healing. Hypercholesterolemic rabbits underwent bilateral iliac artery endothelial denudation, followed by angioplasty. Messenger ribonucleic acid (RNA) (procollagen types I, III and transforming growth factor [TGF]beta(1)), and bio-histometric composition of iliac arteries of animals treated with DEX (2, 7 and 7 days; 1 mg/kg(1)/day(1)), were compared to that in controls 2, 7 and 30 days after angioplasty. Type I and III procollagen mRNA transcripts were up-regulated following injury in either group. Similarly, TGF beta(1), mRNA levels were also elevated; however, treatment with DEX led to down-regulation at day 30 post-angioplasty. Linear regression and correlation of the densitometric ratios of procollagen alpha(1)(I) and TGF beta(1) mRNA during repair were observed significantly in either group (DEX-treated, r(2) = 0.84; non-treated, r(2) = 0.79). Biochemically derived total vascular RNA concentration decreased transiently (7 days), with DEX-treatment (P = 0.003). Arterial lumen cross-sectional area was reduced between days 2 and 30 (P = <0.02), accompanied by an increase in fibrillar collagen concentration in both groups of animals postangioplasty. These results suggest that during barotrauma repair, administration of DEX (similar to 1 week), does not affect vascular intimal hyperplasia or fibrosis, and that despite treatment, significant production of type I procollagen mRNA continues, influencing subsequent collagen deposition, The data also confirm a strong correlation between TGF beta(1) and type I procollagen mRNA expression, and modestly with type III procollagen during post-angioplasty repair. (C) 1997 Academic Press Limited.