PURPOSE: The venous limb of arteriovenous fistulae (AVF) adapts to the arterial environment by dilation and wall thickening; however, the temporal regulation of the expression of extracellular matrix (ECM) components in the venous limb of the maturing AVF has not been well characterized. We used a murine model of AVF maturation that recapitulates human AVF maturation to determine the temporal pattern of expression of these ECM components. METHODS: Aortocaval fistulae were created in C57BL/6J mice and the venous limb was analyzed on postoperative days 1, 3, 7, 21, and 42. A gene microarray analysis was performed on day 7; results were confirmed by qPCR, histology, and immunohistochemistry. Proteases, protease inhibitors, collagens, glycoproteins, and other non-collagenous proteins were characterized. RESULTS: The maturing AVF has increased expression of many ECM components, including increased collagen and elastin. Matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinase 1 (TIMP1) showed increased mRNA and protein expression during the first 7 days of maturation. Increased collagen and elastin expression was also significant at day 7. Expression of structural proteins was increased later during AVF maturation. Osteopontin (OPN) expression was increased at day 1 and sustained during AVF maturation. CONCLUSIONS: During AVF maturation, there is significantly increased expression of ECM components, each of which shows distinct temporal patterns during AVF maturation. Increased expression of regulatory proteins such as MMP and TIMP precedes increased expression of structural proteins such as collagen and elastin, potentially mediating a controlled pattern of ECM degradation and vessel remodeling without structural failure.
PURPOSE: The venous limb of arteriovenous fistulae (AVF) adapts to the arterial environment by dilation and wall thickening; however, the temporal regulation of the expression of extracellular matrix (ECM) components in the venous limb of the maturing AVF has not been well characterized. We used a murine model of AVF maturation that recapitulates human AVF maturation to determine the temporal pattern of expression of these ECM components. METHODS:Aortocaval fistulae were created in C57BL/6J mice and the venous limb was analyzed on postoperative days 1, 3, 7, 21, and 42. A gene microarray analysis was performed on day 7; results were confirmed by qPCR, histology, and immunohistochemistry. Proteases, protease inhibitors, collagens, glycoproteins, and other non-collagenous proteins were characterized. RESULTS: The maturing AVF has increased expression of many ECM components, including increased collagen and elastin. Matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinase 1 (TIMP1) showed increased mRNA and protein expression during the first 7 days of maturation. Increased collagen and elastin expression was also significant at day 7. Expression of structural proteins was increased later during AVF maturation. Osteopontin (OPN) expression was increased at day 1 and sustained during AVF maturation. CONCLUSIONS: During AVF maturation, there is significantly increased expression of ECM components, each of which shows distinct temporal patterns during AVF maturation. Increased expression of regulatory proteins such as MMP and TIMP precedes increased expression of structural proteins such as collagen and elastin, potentially mediating a controlled pattern of ECM degradation and vessel remodeling without structural failure.
Authors: Thomas S Huber; C Keith Ozaki; Timothy C Flynn; W Anthony Lee; Scott A Berceli; Christa M Hirneise; Lori M Carlton; Jeffrey W Carter; Edward A Ross; James M Seeger Journal: J Vasc Surg Date: 2002-09 Impact factor: 4.268
Authors: W R W Wilson; M Anderton; E C Choke; J Dawson; I M Loftus; M M Thompson Journal: Eur J Vasc Endovasc Surg Date: 2008-01-15 Impact factor: 7.069
Authors: Anton N Sidawy; Lawrence M Spergel; Anatole Besarab; Michael Allon; William C Jennings; Frank T Padberg; M Hassan Murad; Victor M Montori; Ann M O'Hare; Keith D Calligaro; Robyn A Macsata; Alan B Lumsden; Enrico Ascher Journal: J Vasc Surg Date: 2008-11 Impact factor: 4.268
Authors: Akihito Muto; Tai Yi; Kenneth D Harrison; Alberto Dávalos; Tiffany T Fancher; Kenneth R Ziegler; Amanda Feigel; Yuka Kondo; Toshiya Nishibe; William C Sessa; Alan Dardik Journal: J Exp Med Date: 2011-02-21 Impact factor: 14.307
Authors: Laisel Martinez; Juan C Duque; Marwan Tabbara; Angela Paez; Guillermo Selman; Diana R Hernandez; Chad A Sundberg; Jason Chieh Sheng Tey; Yan-Ting Shiu; Alfred K Cheung; Michael Allon; Omaida C Velazquez; Loay H Salman; Roberto I Vazquez-Padron Journal: J Am Soc Nephrol Date: 2018-01-02 Impact factor: 10.121
Authors: Daniel J Wong; Daniel Y Lu; Clinton D Protack; Go Kuwahara; Hualong Bai; Nirvana Sadaghianloo; George Tellides; Alan Dardik Journal: J Vasc Surg Date: 2014-10-24 Impact factor: 4.268
Authors: Nirvana Sadaghianloo; Kota Yamamoto; Hualong Bai; Masayuki Tsuneki; Clinton D Protack; Michael R Hall; Serge Declemy; Réda Hassen-Khodja; Joseph Madri; Alan Dardik Journal: Ann Vasc Surg Date: 2017-02-03 Impact factor: 1.466
Authors: Go Kuwahara; Takuya Hashimoto; Masayuki Tsuneki; Kota Yamamoto; Roland Assi; Trenton R Foster; Jesse J Hanisch; Hualong Bai; Haidi Hu; Clinton D Protack; Michael R Hall; John S Schardt; Steven M Jay; Joseph A Madri; Shohta Kodama; Alan Dardik Journal: Arterioscler Thromb Vasc Biol Date: 2017-04-27 Impact factor: 8.311
Authors: Kirstyn E Brownson; Ramak Khosravi; Shin-Rong Lee; Kimberly Goldstein; Toshihiko Isaji; Shun Ono; Clinton D Protack; Jay D Humphrey; Alan Dardik Journal: J Surg Res Date: 2019-12-31 Impact factor: 2.192