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.
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.
Authors: Yann Gouëffic; Susan Potter-Perigo; Christina K Chan; Pamela Y Johnson; Kathleen Braun; Steven P Evanko; Thomas N Wight Journal: Atherosclerosis Date: 2006-12-14 Impact factor: 5.162
Authors: Heleen Rienstra; Kirankumar Katta; Johanna W A M Celie; Harry van Goor; Gerjan Navis; Jacob van den Born; Jan-Luuk Hillebrands Journal: PLoS One Date: 2010-02-05 Impact factor: 3.240
Authors: Jerzy Krupinski; Priya Ethirajan; M Angels Font; Marta Miguel Turu; John Gaffney; Pat Kumar; Mark Slevin Journal: Biomark Insights Date: 2008-05-12