COLLAGEN CONTENT IS SIGNIFICANTLY LOWER IN RESTENOTIC VERSUS NONRESTENOTIC VESSELS AFTER BALLOON ANGIOPLASTY IN THE ATHEROSCLEROTIC RABBIT MODEL

Background it is recognized that restenosis is primarily due to altera tions in geometric remodeling of the extracellular matrix rather than intimal hyperplasia. Prior studies have shown that angioplasty stimula tes an increase in both synthesis and degradation of collagen in the a therosclerotic vessel. However, differences in collagen content and me tabolism between restenotic and nonrestenotic vessels have not been ex amined. Methods and Results Four weeks after angioplasty in an atheros clerotic rabbit model, collagen content in restenotic and nonrestenoti c vessels was measured both biochemically by hydroxyproline quantitati on and histologically by a digital subtraction method with the use of circularly polarized images of picrosirius red-stained sections. Colla genase and gelatinase activity also were measured in the same restenot ic and nonrestenotic vessels by use of a radiosubstrate assay. Collage n content was found to be significantly lower in restenotic vessels th an in nonrestenotic vessels both biochemically (127.0+/-32.6 versus 21 2.6+/-84.3 mu g/mg tissue; n=11 vessels; P<.05) and histologically (67 .3+/-7.9% versus 76.3+/-11.8% area fraction; n=20 sections from 6 vess els; P=.05). There was a significant inverse correlation between bioch emically determined collagen content and gelatinase activity (P=.02) a nd a significant correlation between histologically determined lumen a rea and percent collagen content (P =.0071). Conclusions Collagen cont ent is significantly decreased in restenotic versus nonrestenotic vess els after angioplasty in the atherosclerotic rabbit model. The increas ed collagen content in nonrestenotic vessels was associated with prese rved lumen area and may play a role in geometric remodeling after angi oplasty.