title: Development of pseudointima and stenosis after transjugular intrahepatic portasystemic shunts: characterization of cell phenotype and function.
abstract: The clinical utility of transjugular intrahepatic portasystemic shunts (TIPS) is frequently complicated by the ingrowth of tissue into the stent lumen, causing stent stenosis. These studies were undertaken to define the cellular and matrix components of the pseudointima, define the phenotype and function of the mesenchymal cells in the pseudointima and maintain them in culture, and to study the differences between stenotic and nonstenosed stents. A total of 35 stents were evaluated. TIPS pseudointima were examined histologically, by immunohistochemistry and in situ hybridization to determine the cellular and connective tissue constituents. Mesenchymal cells were grown from tissue within the TIPS and around it, and their phenotype was studied and compared with control smooth muscle cells and fibroblasts. Masson's trichrome staining of histological sections demonstrated that TIPS tissue was composed of collagen and palisades of mesenchymal cells and was lined by an endothelium. Immunostaining demonstrated strong and uniform alpha-smooth muscle staining in TIPS mesenchymal cells and peri-TIPS cells. Type I procollagen mRNA expression was demonstrated in mesenchymal cells in and around the stent by in situ hybridization. TIPS mesenchymal cells secreted less radiolabeled fibronectin, and far more type III, relative to type I, collagen compared with peri-TIPS cells. TIPS cells also expressed high levels of type III procollagen mRNA compared with peri-TIPS cells. There was no difference between stenotic stents and nonstenosed stents with respect to clinical features, time from stenting, gross morphology, histology, presence of bile fistulae, and cell phenotype. However, smooth muscle cells (SMC) from stenotic stents demonstrated both greater cell proliferation and collagen I and III secretion compared with those from nonstenosed stents. These data demonstrate that TIPS stenosis results from an accumulation of collagen and proliferation of SMC within the stent lumen.
authors.affiliation: Division of Gastroenterology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0341, USA.
authors.forename: A J
authors.initials: AJ
authors.lastname: Sanyal
authors.forename: M J
authors.initials: MJ
authors.lastname: Contos
authors.forename: D
authors.initials: D
authors.lastname: Yager
authors.forename: Y N
authors.initials: YN
authors.lastname: Zhu
authors.forename: A
authors.initials: A
authors.lastname: Willey
authors.forename: M F
authors.initials: MF
authors.lastname: Graham
mesh_terms: D002478:Cells, Cultured; D003251:Constriction, Pathologic; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008648:Mesoderm / Q000378:metabolism / Q000473:pathology / Q000502:physiology; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D010641:Phenotype; D019168:Portasystemic Shunt, Transjugular Intrahepatic / Q000009:adverse effects*; D011347:Procollagen / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017539:Tunica Intima / Q000254:growth & development / Q000473:pathology*
chemical_list: D011347:Procollagen; D012333:RNA, Messenger