Hualong Bai1, Jung Seok Lee1, Haidi Hu1, Tun Wang1, Toshihiko Isaji1, Shirley Liu1, Jianming Guo1, Haiyang Liu1, Katharine Wolf1, Shun Ono1, Xiangjiang Guo1, Bogdan Yatsula1, Ying Xing1, Tarek M Fahmy1, Alan Dardik2. 1. From the Department of Vascular Surgery, First Affiliated Hospital of Zhengzhou University, Henan, China (H.B.); Basic Medical College of Zhengzhou University, Henan, China (H.B., Y.X.); Vascular Biology and Therapeutics Program (H.B., H.H., T.W., T.I., S.L., J.G., H.L., K.W., S.O., X.G., B.Y., A.D.), Department of Surgery (H.B., H.H., T.W., T.I., S.L., J.G., H.L., K.W., S.O., X.G., B.Y., A.D.), and Department of Immunobiology (T.M.F.), Yale University School of Medicine, New Haven, CT; Department of Biomedical Engineering, Yale University, New Haven, CT (J.S.L., T.M.F.); and Department of Surgery, VA Connecticut Healthcare System, West Haven, CT (A.D.). 2. From the Department of Vascular Surgery, First Affiliated Hospital of Zhengzhou University, Henan, China (H.B.); Basic Medical College of Zhengzhou University, Henan, China (H.B., Y.X.); Vascular Biology and Therapeutics Program (H.B., H.H., T.W., T.I., S.L., J.G., H.L., K.W., S.O., X.G., B.Y., A.D.), Department of Surgery (H.B., H.H., T.W., T.I., S.L., J.G., H.L., K.W., S.O., X.G., B.Y., A.D.), and Department of Immunobiology (T.M.F.), Yale University School of Medicine, New Haven, CT; Department of Biomedical Engineering, Yale University, New Haven, CT (J.S.L., T.M.F.); and Department of Surgery, VA Connecticut Healthcare System, West Haven, CT (A.D.). alan.dardik@yale.edu.
Abstract
OBJECTIVE: Pseudoaneurysms remain a significant complication after vascular procedures. We hypothesized that TGF-β (transforming growth factor-β) signaling plays a mechanistic role in the development of pseudoaneurysms. APPROACH AND RESULTS: Rat aortic pericardial patch angioplasty was associated with a high incidence (88%) of pseudoaneurysms at 30 days, with increased smad2 phosphorylation in small pseudoaneurysms but not in large pseudoaneurysms; TGF-β1 receptors were increased in small pseudoaneurysms and preserved in large pseudoaneurysms. Delivery of TGF-β1 via nanoparticles covalently bonded to the patch stimulated smad2 phosphorylation both in vitro and in vivo and significantly decreased pseudoaneurysm formation (6.7%). Inhibition of TGF-β1 signaling with SB431542 decreased smad2 phosphorylation both in vitro and in vivo and significantly induced pseudoaneurysm formation by day 7 (66.7%). CONCLUSIONS: Normal healing after aortic patch angioplasty is associated with increased TGF-β1 signaling, and recruitment of smad2 signaling may limit pseudoaneurysm formation; loss of TGF-β1 signaling is associated with the formation of large pseudoaneurysms. Enhancement of TGF-β1 signaling may be a potential mechanism to limit pseudoaneurysm formation after vascular intervention.
OBJECTIVE:Pseudoaneurysms remain a significant complication after vascular procedures. We hypothesized that TGF-β (transforming growth factor-β) signaling plays a mechanistic role in the development of pseudoaneurysms. APPROACH AND RESULTS:Rat aortic pericardial patch angioplasty was associated with a high incidence (88%) of pseudoaneurysms at 30 days, with increased smad2 phosphorylation in small pseudoaneurysms but not in large pseudoaneurysms; TGF-β1 receptors were increased in small pseudoaneurysms and preserved in large pseudoaneurysms. Delivery of TGF-β1 via nanoparticles covalently bonded to the patch stimulated smad2 phosphorylation both in vitro and in vivo and significantly decreased pseudoaneurysm formation (6.7%). Inhibition of TGF-β1 signaling with SB431542 decreased smad2 phosphorylation both in vitro and in vivo and significantly induced pseudoaneurysm formation by day 7 (66.7%). CONCLUSIONS: Normal healing after aortic patch angioplasty is associated with increased TGF-β1 signaling, and recruitment of smad2 signaling may limit pseudoaneurysm formation; loss of TGF-β1 signaling is associated with the formation of large pseudoaneurysms. Enhancement of TGF-β1 signaling may be a potential mechanism to limit pseudoaneurysm formation after vascular intervention.
Authors: F Werner; M K Jain; M W Feinberg; N E Sibinga; A Pellacani; P Wiesel; M T Chin; J N Topper; M A Perrella; M E Lee Journal: J Biol Chem Date: 2000-11-24 Impact factor: 5.157
Authors: Matthew A Dale; Wanfen Xiong; Jeffrey S Carson; Melissa K Suh; Andrew D Karpisek; Trevor M Meisinger; George P Casale; B Timothy Baxter Journal: J Immunol Date: 2016-05-04 Impact factor: 5.422
Authors: Aida M Bertoli-Avella; Elisabeth Gillis; Hiroko Morisaki; Judith M A Verhagen; Bianca M de Graaf; Gerarda van de Beek; Elena Gallo; Boudewijn P T Kruithof; Hanka Venselaar; Loretha A Myers; Steven Laga; Alexander J Doyle; Gretchen Oswald; Gert W A van Cappellen; Itaru Yamanaka; Robert M van der Helm; Berna Beverloo; Annelies de Klein; Luba Pardo; Martin Lammens; Christina Evers; Koenraad Devriendt; Michiel Dumoulein; Janneke Timmermans; Hennie T Bruggenwirth; Frans Verheijen; Inez Rodrigus; Gareth Baynam; Marlies Kempers; Johan Saenen; Emeline M Van Craenenbroeck; Kenji Minatoya; Ritsu Matsukawa; Takuro Tsukube; Noriaki Kubo; Robert Hofstra; Marie Jose Goumans; Jos A Bekkers; Jolien W Roos-Hesselink; Ingrid M B H van de Laar; Harry C Dietz; Lut Van Laer; Takayuki Morisaki; Marja W Wessels; Bart L Loeys Journal: J Am Coll Cardiol Date: 2015-04-07 Impact factor: 24.094
Authors: Ying H Shen; Scott A LeMaire; Nancy R Webb; Lisa A Cassis; Alan Daugherty; Hong S Lu Journal: Arterioscler Thromb Vasc Biol Date: 2020-03-25 Impact factor: 8.311
Authors: Hong S Lu; Ann Marie Schmidt; Robert A Hegele; Nigel Mackman; Daniel J Rader; Christian Weber; Alan Daugherty Journal: Arterioscler Thromb Vasc Biol Date: 2019-12-23 Impact factor: 8.311