title: In-stent restenosis is associated with neointimal angiogenesis and macrophage infiltrates.
abstract: Restenosis after stenting occurs secondary to the neointima formation. Neovessels have been found in the neointima within stents. However, there are few studies correlating neointimal angiogenesis and in-stent restenosis in humans. We analyzed 65 post-mortem stented arteries from 33 patients with duration >3 months. Cause of death was determined incidental to the coronary findings in every case. Stented segments were embedded in paraffin and stained immunohistochemically for CD68 (macrophages), and endothelial marker PECAM-1 (CD31). Computerized morphometry was performed to quantitate neovessel density for CD31, macrophage infiltrates, as well as plaque and neointimal area. In-stent restenosis was defined as luminal narrowing ≥ 75% cross-section of the stented area. Underlying plaque morphology was classified as fibrous or atheromatous. Neovessels were present in the neointima of 57 stented segments (88%). Mean neovessel density was greater in restenotic vs. non-restenotic neointimas (p = 0.009) and macrophage density was also greater (p = 0.006). Neointimal area correlated positively with density of neointimal vessels (p = 0.002), as well as neointimal macrophage density (p = 0.006), but not type of stent, underlying plaque type, or underlying plaque macrophage score. We conclude that in-stent restenosis is associated with neointimal angiogenesis which is accompanied by macrophage inflammation. The relevance of these findings to treatment and prevention of in-stent restenosis needs to be further explored.
authors.affiliation: Department of Forensic Medicine, Shanghai Medical College, Fudan University, Shanghai 20032, China; University of Maryland Medical System, Baltimore, MD 20201, USA.
authors.forename: MingChang
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Georgetown University Hospital, Washington, DC 20007, USA.
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Cresswell
authors.affiliation: Messejana Heart and Lung Hospital, Fortaleza 4023-900, Brazil.
authors.forename: Fabio
authors.initials: F
authors.lastname: Tavora
authors.affiliation: Nova Scotia Medical Examiner Service, Halifax, Nova Scotia, Canada B3J 2L1.
authors.forename: Erik
authors.initials: E
authors.lastname: Mont
authors.affiliation: Department of Forensic Medicine, Shanghai Medical College, Fudan University, Shanghai 20032, China.
authors.forename: Ziqin
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Department of Forensic Medicine, Shanghai Medical College, Fudan University, Shanghai 20032, China; University of Maryland Medical System, Baltimore, MD 20201, USA. Electronic address: aburke@umm.edu.
authors.forename: Allen
authors.initials: A
authors.lastname: Burke
mesh_terms: D023903:Coronary Restenosis / Q000473:pathology*; D003331:Coronary Vessels / Q000473:pathology* / Q000601:surgery; D005260:Female; D006801:Humans; D008264:Macrophages / Q000473:pathology*; D008297:Male; D058426:Neointima / Q000473:pathology* / Q000601:surgery; D009389:Neovascularization, Pathologic / Q000473:pathology*; D058226:Plaque, Atherosclerotic / Q000473:pathology* / Q000601:surgery; D012042:Registries; D015607:Stents / Q000009:adverse effects
keywords: In-stent restenosis; Macrophage inflammation; Neointimal angiogenesis