Balloon Angioplasty Significantly Increases Collagen Content but Does not Alter Collagen Subtype I /III Ratios in the Atherosclerotic Rabbit Iliac Model

Angioplasty has been reported to increase collagen content and to alter vascular collagenα1(I),α2(I), andα1(III) mRNA levels. Collagen synthesis is tightly regulated by complex translational and post-translational mechanisms such that mRNA levels may not necessarily reflect biosynthesis. To test whether collagen subtype I and III protein levels are altered by angioplasty, we quantitatively analysed collagen I /III protein ratios at 4 weeks after balloon angioplasty. Twenty New Zealand White rabbits underwent iliac artery balloon de-endothelialization and then were placed on a 0.5 % cholesterol /6 % peanut oil diet for 7 weeks at which time angioplasty was performed on arteries with ≥50 % stenosis. Arteries with <50 % stenosis were not dilated and served as controls. Animals were killed 4 weeks later and hydroxyproline (OH-pro) content and subtype I /III ratios were analysed in 5-mm mid-iliac sections. OH-pro was measured by a colorimetric assay. Subtype ratios were determined by a highly quantitative two-dimensional cyanogen bromide peptide mapping method. The degree of stenosis was measured as the minimal vessel lumen diameter and calculated as a percentage stenosis compared to a proximal reference segment. Calculated collagen content (μg /mg tissue) was significantly higher 4 weeks following angioplasty compared to the non-dilated group (220.4 ±70.8v308.2 ±26.9,P=0.04;n=12), despite similar percentage stenosis in the primary and restenotic lesions. The ratio of collagen I /III subtype protein distribution was not significantly different in the non-dilated and angioplastied groups (4.88 ±1.00v4.70 ±0.82, respectively). These studies are the first to provide data on collagen I /III subtypes following angioplasty and suggest that collagen accumulation may be more important in restenosis than alteration of collagen protein subtypes.