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]beta1), and bio-histometric composition of iliac arteries of animals treated with DEX (2, 7 and 7 days; 1 mg/kg1/day1), 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, TGFbeta1 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 alpha1(I) and TGFbeta1 mRNA during repair were observed significantly in either group (DEX-treated, r2= 0.84; non-treated, r2=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 post-angioplasty. These results suggest that during barotrauma repair, administration of DEX (approximately 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 TGFbeta1 and type I procollagen mRNA expression, and modestly with type III procollagen during post-angioplasty repair.
Karim
M A
MA
Department of Medicine, University of Texas Southwestern, Dallas Veterans Affair Medical Center, 75216, USA.
Frizzell
S
S
Inman
L
L
Shinn
M
M
Miller
D D
DD
D017130:Angioplasty; D000818:Animals; D001469:Barotrauma / Q000188:drug therapy* / Q000601:surgery; D001808:Blood Vessels / Q000293:injuries* / Q000378:metabolism / Q000473:pathology*; D003430:Cross-Sectional Studies; D004247:DNA / Q000737:chemistry / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology; D005355:Fibrosis / Q000188:drug therapy / Q000601:surgery; D005938:Glucocorticoids / Q000494:pharmacology* / Q000627:therapeutic use; D006909:Hydroxyproline / Q000737:chemistry / Q000187:drug effects; D016014:Linear Models; D008297:Male; D011347:Procollagen / Q000235:genetics; D011506:Proteins / Q000737:chemistry / Q000187:drug effects; D012313:RNA / Q000737:chemistry / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis; D011817:Rabbits; D016212:Transforming Growth Factor beta / Q000235:genetics
D005938:Glucocorticoids; D011347:Procollagen; D011506:Proteins; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D012313:RNA; D003907:Dexamethasone; D004247:DNA; D006909:Hydroxyproline