title: Relation of Internal Elastic Lamellar Layer Disruption to Neointimal Cellular Proliferation and Type III Collagen Deposition in Human Peripheral Artery Restenosis.
abstract: Smooth muscle cell proliferation and extracellular matrix formation are responsible for disease progression in de novo and restenotic atherosclerosis. Internal elastic lamella (IEL) layer maintains the structural integrity of intima, and disruption of IEL may be associated with alterations in neointima, type III collagen deposition, and lesion progression in restenosis. Nineteen restenotic plaques (12 patients) procured during peripheral interventions were compared with 13 control plaques (12 patients) without restenosis. Hematoxylin & Eosin and elastic trichrome stains were used to measure length and percentage of IEL disruption, cellularity, and inflammation score. Type I and III collagens, smooth muscle cell (smc), fibroblast density, and nuclear proliferation (Ki67) percentage were evaluated by immunohistochemistry. IEL disruption percentage (28 ± 3.6 vs 6.1 ± 2.4; p = 0.0006), type III collagen content (0.33 ± 0.06 vs 0.17 ± 0.07; p = 0.0001), smc density (2014 ± 120 vs 923 ± 150; p = 0.0001), fibroblast density (2,282 ± 297 vs 906 ± 138; p = 0.0001), and Ki67 percentage (21.6 ± 2 vs 8.2 ± 0.65; p = 0.0001) were significantly increased in restenotic plaques compared to de novo plaques. Logistic regression analysis identified significant correlation between IEL disruption and neointimal smc density (r = 0.45; p = 0.01) and with type III collagen deposition (r = 0.61; p = 0.02) in restenosis. Increased IEL disruption may trigger cellular proliferation, altering collagen production, and enhancing restenotic neointima. In conclusion, understanding the pathologic and molecular basis of restenosis and meticulous-guided interventions oriented to minimize IEL damage may aid to reduce neointimal proliferation and the occurrence of restenosis.
authors: Department of Medicine/Cardiology, The Zena and Michael A. Weiner Cardiovascular Institute and the Marie-Josée and Henry R. Kravis Cardiovascular Health Center, Icahn School of Medicine at Mount Sinai, New York, New York.
authors: Prakash
authors: P
authors: Krishnan
authors: Department of Medicine/Cardiology, The Zena and Michael A. Weiner Cardiovascular Institute and the Marie-Josée and Henry R. Kravis Cardiovascular Health Center, Icahn School of Medicine at Mount Sinai, New York, New York. Electronic address: purushothaman.kothandaraman@mountsinai.org.
authors: K-Raman
authors: KR
authors: Purushothaman
authors: Department of Medicine/Cardiology, The Zena and Michael A. Weiner Cardiovascular Institute and the Marie-Josée and Henry R. Kravis Cardiovascular Health Center, Icahn School of Medicine at Mount Sinai, New York, New York.
authors: Meerarani
authors: M
authors: Purushothaman
authors: Department of Medicine/Cardiology, The Zena and Michael A. Weiner Cardiovascular Institute and the Marie-Josée and Henry R. Kravis Cardiovascular Health Center, Icahn School of Medicine at Mount Sinai, New York, New York.
authors: Usman
authors: U
authors: Baber
authors: Department of Medicine/Cardiology, The Zena and Michael A. Weiner Cardiovascular Institute and the Marie-Josée and Henry R. Kravis Cardiovascular Health Center, Icahn School of Medicine at Mount Sinai, New York, New York.
authors: Arthur
authors: A
authors: Tarricone
authors: Department of Medicine/Cardiology, The Zena and Michael A. Weiner Cardiovascular Institute and the Marie-Josée and Henry R. Kravis Cardiovascular Health Center, Icahn School of Medicine at Mount Sinai, New York, New York.
authors: Miguel
authors: M
authors: Vasquez
authors: Department of Medicine/Cardiology, The Zena and Michael A. Weiner Cardiovascular Institute and the Marie-Josée and Henry R. Kravis Cardiovascular Health Center, Icahn School of Medicine at Mount Sinai, New York, New York.
authors: Jose
authors: J
authors: Wiley
authors: Department of Medicine/Cardiology, The Zena and Michael A. Weiner Cardiovascular Institute and the Marie-Josée and Henry R. Kravis Cardiovascular Health Center, Icahn School of Medicine at Mount Sinai, New York, New York.
authors: Annapoorna
authors: A
authors: Kini
authors: Department of Medicine/Cardiology, The Zena and Michael A. Weiner Cardiovascular Institute and the Marie-Josée and Henry R. Kravis Cardiovascular Health Center, Icahn School of Medicine at Mount Sinai, New York, New York.
authors: Samin K
authors: SK
authors: Sharma
authors: Department of Pathology and Laboratory Medicine, University of Kentucky Medical Center, Lexington, Kentucky.
authors: William N
authors: WN
authors: O'Connor
authors: Department of Medicine/Cardiology, The Zena and Michael A. Weiner Cardiovascular Institute and the Marie-Josée and Henry R. Kravis Cardiovascular Health Center, Icahn School of Medicine at Mount Sinai, New York, New York.
authors: Pedro R
authors: PR
authors: Moreno
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D049109:Cell Proliferation; D024061:Collagen Type III / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D058426:Neointima / Q000473:pathology*; D058729:Peripheral Arterial Disease / Q000209:etiology / Q000378:metabolism* / Q000473:pathology*; D011651:Pulmonary Artery; D012008:Recurrence; D012307:Risk Factors
chemical_list: D024061:Collagen Type III