Luminally polarized mural and vascular remodeling in ileal strictures of Crohn's disease Journal Article


Authors: Zhang, X.; Ko, H. M.; Torres, J.; Panchal, H. J.; Cai, Z.; Wagner, M.; Sands, B. E.; Colombel, J. F.; Cho, J.; Taouli, B.; Harpaz, N.
Article Title: Luminally polarized mural and vascular remodeling in ileal strictures of Crohn's disease
Abstract: Intestinal stricture, a major complication of Crohn's disease (CD), results from fibromuscular remodeling and expansion of the intestinal wall. The corresponding microanatomical alterations have not been fully described, hindering progress toward understanding their pathogenesis and devising appropriate treatments. We used tissue-specific staining and quantitative digital histomorphometry for this purpose. Serial histologic sections from 37 surgically resected ileal strictures and adjacent nonstrictured controls from patients with CD were evaluated after staining for smooth muscle actin, collagen (Sirius red), and collagen types I, III, and V. Overall mural thickening in strictures was increased 2.2 ± 0.2-fold compared with nonstrictured regions of the same specimens. The muscular layer most altered was the muscularis mucosae (MM). Compared with the internal and external layers of the muscularis propria, (MP) which were expanded 1.9 ± 0.2- and 1.3 ± 0.1-fold, respectively, the MM was expanded 17.7 ± 2.6-fold, reflecting the combined effects of architectural disarray, an 11.6 ± 1.4-fold increase smooth muscle content, and elaboration of pericellular type V collagen. In contrast, the architecture of the MP was preserved and pericellular collagen was virtually absent; rather, fibrosis in this layer was limited to expansion of the intramuscular septa by collagen types I and III. The muscular arteries and veins within the strictured submucosa frequently exhibited eccentric, luminally oriented adventitial mantles comprising hyperplastic myocytes and extracellular type V collagen. We conclude that the fibromuscular remodeling which results in CD-associated ileal strictures predominantly involves the MM and submucosal vasculature in a luminally polarized fashion and suggests that mucosal-based factors may contribute to stricture pathogenesis. © 2018
Keywords: immunohistochemistry; adolescent; adult; clinical article; controlled study; human tissue; protein expression; aged; histopathology; pathogenesis; collagen type 1; tissue section; fibrosis; correlation analysis; quantitative analysis; staining; clinical evaluation; collagen; vasculopathy; cell hyperplasia; intestine muscle; crohn's disease; crohn disease; smooth muscle; collagen type 3; collagen type 5; intestine mucosa; muscle cell; smooth muscle actin; artery; vein; vascular remodeling; submucosa; stricture; muscularis mucosa; intestine wall; human; male; female; article; morphometry; muscularis mucosae; intestine stenosis; digital morphometry; type v collagen; ileal stricture
Journal Title: Human Pathology
Volume: 79
ISSN: 0046-8177
Publisher: Elsevier Inc.  
Date Published: 2018-09-01
Start Page: 42
End Page: 49
Language: English
DOI: 10.1016/j.humpath.2018.03.004
PROVIDER: scopus
PUBMED: 29555578
DOI/URL:
Notes: Article -- Export Date: 1 August 2018 -- Source: Scopus
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  1. Hinaben J Panchal
    15 Panchal