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(Circulation. 2004;110:940-947.)
© 2004 American Heart Association, Inc.

Original Articles

Extracellular Matrix Changes in Stented Human Coronary Arteries

Andrew Farb, MD; Frank D. Kolodgie, PhD; Jin-Yong Hwang, MD, PhD; Allen P. Burke, MD; Kirubel Tefera, BSc; Deena K. Weber, MS; Thomas N. Wight, PhD; Renu Virmani, MD

From the Department of Cardiovascular Pathology, Armed Forces Institute of Pathology, Washington, DC (A.F., F.D.K., A.P.B., K.T., D.K.W., R.V.); the Hope Heart Institute, Seattle, Wash (T.N.W., J.-Y.H.); and Gyeongsang National University, Jinju, Korea (J.-Y.H.).

Correspondence to Renu Virmani, MD, Department of Cardiovascular Pathology, Armed Forces Institute of Pathology, Washington, DC 20306-6000. E-mail Virmani{at}afip.osd.mil

Received March 5, 2004; revision received April 29, 2004; accepted May 3, 2004.

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 3 to <9 months (n=17) were assigned to group 1, stents 9 to <18 months old (n=19) to group 2, and stents 18 months old (n=9) to group 3. In groups 1 and 2, neointimal versican and hyaluronan staining was strongly positive, colocalized with -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.

Key Words: atherosclerosis • pathology • restenosis • stents

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