(Circulation. 1995;91:2049-2057.)
© 1995 American Heart Association, Inc.
Articles |
Histomorphometric and Biochemical Correlates of Arterial Procollagen Gene Expression During Vascular Repair After Experimental Angioplasty
Presented in part at the 42nd Annual Scientific Session of the American College of Cardiology (Young Investigator's Award), March 1993, Anaheim, Calif.
From the Departments of Medicine and Pathology, St Louis University School of Medicine and Department of Medicine, Loyola University Stritch School of Medicine, St Louis, Mo.
Correspondence to D. Douglas Miller, MD, Associate Professor of Medicine, St Louis University Medical Center, Division of Cardiology, 3635 Vista Ave at Grand Blvd, PO Box 15250, St Louis, MO 63110-0250.
Background To determine the transcriptional,
biochemical, and histomorphometric correlates of neointimal
procollagen accumulation during arterial repair after balloon
angioplasty of atherogenic vessels, rabbit iliac artery collagen
content and the induction of 
1(I) and
1(III) procollagen mRNA were assessed in normal vessels
and at 2, 7, and 30 days after angioplasty.
Methods and Results Quantitative iliac artery histomorphometric
neointimal collagen analysis was performed using a
specific picrosirius red stain under polarized light. Arterial
cross-sectional area reduction, total cellularity, and vascular smooth
muscle cell density (per 104 µ2 of
neointima) were quantified in routine and
immunohistochemically stained sections (-actin and RAM-11), from
which biochemical concentrations of tissue protein, RNA, and DNA were
also measured. Collagen comprised 0.23±0.1 mg/mg of total protein in
the normal vessel wall and did not increase in vessels studied 2 and 7
days after angioplasty (0.26±0.06, 0.28±0.05 mg/mg of protein,
P=NS). By 30 days after angioplasty, >50% of the protein
concentration was collagen (0.55±0.11 mg/mg of protein,
P=.02). Collagen-positive histological staining also
increased significantly from 17±2% of the neointima at
day 2 to 32±5% by day 30 (P=.01). The transcript
regulatory signal for 1(I) procollagen mRNA was induced
2 days after angioplasty, peaking at 7 days for both
1(I) and 1(III), and returning to control
levels 30 days after angioplasty. A significant luminal cross-sectional
area reduction of the arterial wall was confirmed both by angiography
and histomorphometry (P=.01). This was not associated with a
significant change in -actin (+) vascular smooth muscle cell density
(38±7 nuclei per 104µ2 at day 2 and at day
30) or tissue DNA concentration (P=NS).
Conclusions We conclude that procollagen genes are transcriptionally activated early (2 to 7 days) after angioplasty vessel injury and that collagen subsequently constitutes a major biochemical and histological component of the proliferative neointima by 30 days after angioplasty. Alterations in pathways regulating procollagen metabolism may also contribute to the accumulation of extracellular matrix and growth of the neointima in the late repair phase after vessel wall injury.
Key Words: angioplasty • endothelium • genes
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