Small leucine-rich proteoglycans in atherosclerotic lesions: novel targets of chronic statin treatment?
Bottom Line: Furthermore, matrix metalloproteinase 2 and gelatinolytic activity were decreased in response to rosuvastatin and a condensed collagen-rich matrix was formed.In carotid endarterectomy specimens of statin-treated patients increased decorin and biglycan accumulation was detected as well.Drug treatment did not change low-density lipoprotein (LDL) plasma levels in ApoE-deficient mice and did not significantly affect lipid retention at the aortic root level as demonstrated by oil-red O staining and immunohistochemistry of LDL.
Affiliation: Bundesinstitut für Arzneimittel und Medizinprodukte, Bonn, Germany.Show MeSH
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Mentions: A mechanism that might increase the packing of collagen fibrils as detected in Fig. 1 is the accumulation of the collagen binding SLRPs, decorin and biglycan. As shown in Fig. 2A–C, decorin accumulation analysed by immunostaining was increased throughout the plaque intima including the entire fibrous cap in rosuvastatin-treated animals. Furthermore, decorin was increased also in the medial layer and in the circumference of the aortic root. The immunohistochemical results were supported by Western blot analysis using aortic extracts (Fig. 2G, H). Decorin presented as a typical double band  and was significantly increased in aortic extracts from rosuvastatin treated mice as determined by densitometric scanning of the upper band. In a similar manner to decorin, the accumulation of another collagen binding SLRP, biglycan, was also dramatically increased in the neointima of aortic root lesions (Fig. 2D–F) and in aortic extracts (Fig. 2I, J) as detected by immunohistochemistry and Western blotting, respectively. In contrast to decorin and biglycan, versican and perlecan were not affected by the pharmacological treatment (not shown). In addition, atherosclerotic lesions of innominate arteries that represent vascular lesions were examined. The results were very similar to those achieved from plaques at the aortic root (Fig. 3). Specifically, the amount of tightly arranged collagen was strongly increased as demonstrated by birefringence analysis (Fig. 3D–F) whereas total collagen remained unchanged. Image analysis of biglycan (Fig. 3G–I) and decorin (Fig. 3J–L) showed increased signals of both SLRPs that were even more pronounced as at the aor-tic root (compared to Fig. 2).
Affiliation: Bundesinstitut für Arzneimittel und Medizinprodukte, Bonn, Germany.