Extracellular matrix changes in stented human coronary arteries

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 greater than or equal to 3 to < 9 months ( n = 17) were assigned to group 1, stents >= 9 to < 18 months old ( n = 19) to group 2, and stents greater than or equal to 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.