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  • Title: Extracellular matrix changes in stented human coronary arteries.
    Author: Farb A, Kolodgie FD, Hwang JY, Burke AP, Tefera K, Weber DK, Wight TN, Virmani R.
    Journal: Circulation; 2004 Aug 24; 110(8):940-7. PubMed ID: 15302784.
    Abstract:
    BACKGROUND: Restenosis after stenting occurs secondary to the accumulation of smooth muscle cells (SMCs) and extracellular matrix (ECM), with the ECM accounting for >50% of the neointimal volume. The composition of the in-stent ECM has not been well characterized in humans. METHODS AND RESULTS: Postmortem human coronary arteries (n=45) containing stents underwent histological assessment of neointimal proteoglycans, hyaluronan, collagen (types I and III), SMCs, and CD44 (a cell surface receptor for hyaluronan). The mean duration of stent implantation was 18.7 months; stents in place > or =3 to <9 months (n=17) were assigned to group 1, stents > or =9 to <18 months old (n=19) to group 2, and stents > or =18 months old (n=9) to group 3. In groups 1 and 2, neointimal versican and hyaluronan staining was strongly positive, colocalized with alpha-actin-positive SMCs, and was greater in intensity compared with group 3. Conversely, decorin staining was greatest in group 3. The neointima of both group 1 and 2 stents was rich in type III collagen, with reduced staining in group 3. Type I collagen staining was weakest in group 1 stents, with progressively stronger staining in groups 2 and 3. SMC density and stent stenosis were significantly reduced in group 3 stents compared with groups 1 and 2. CD44 staining colocalized with macrophages and was associated with increased neointimal thickness. CONCLUSIONS: The ECM within human coronary stents resembles a wound that is not fully healed until 18 months after deployment, followed by neointimal retraction. ECM contraction may be a target for therapies aimed at stent restenosis prevention.
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