PURPOSE: A goal of this study was to identify and investigate previously unrecognized components of the remodeling process in the progression to heart failure by comparing protein expression in ischemic failing (F) and nonfailing (NF) human hearts. EXPERIMENTAL DESIGN: Protein expression differences were investigated using multidimensional protein identification and validated by Western analysis. This approach detected basal lamina (BL) remodeling, and further studies analyzed samples for evidence of structural BL remodeling. A rat model of pressure overload (PO) was studied to determine whether nonischemic stressors also produce BL remodeling and impact cellular adhesion. RESULTS: Differential protein expression of collagen IV, laminin α2, and nidogen-1 indicated BL remodeling develops in F versus NF hearts Periodic disruption of cardiac myocyte BL accompanied this process in F, but not NF heart. The rat PO myocardium also developed BL remodeling and compromised myocyte adhesion compared to sham controls. CONCLUSIONS AND CLINICAL RELEVANCE: Differential protein expression and evidence of structural and functional BL alterations develop during heart failure. The compromised adhesion associated with this remodeling indicates a high potential for dysfunctional cellular integrity and tethering in failing myocytes. Therapeutically targeting BL remodeling could slow or prevent the progression of heart disease.
PURPOSE: A goal of this study was to identify and inpan>vestigate previously unrecognized components of the remodeling process in the progression to heart failure by comparing protein expression in ischemic failing (F) and nonfailing (NF) human hearts. EXPERIMENTAL DESIGN: Protein expression differences were investigated using multidimensional protein identification and validated by Western analysis. This approach detected basal lamina (BL) remodeling, and further studies analyzed samples for evidence of structural BL remodeling. A rat model of pressure overload (PO) was studied to determine whether nonischemic stressors also produce BL remodeling and impact cellular adhesion. RESULTS: Differential protein expression of collagen IV, laminin α2, and nidogen-1 indicated BL remodeling develops in F versus NF hearts Periodic disruption of cardiac myocyte BL accompanied this process in F, but not NF heart. The rat PO myocardium also developed BL remodeling and compromised myocyte adhesion compared to sham controls. CONCLUSIONS AND CLINICAL RELEVANCE: Differential protein expression and evidence of structural and functional BL alterations develop during heart failure. The compromised adhesion associated with this remodeling indicates a high potential for dysfunctional cellular integrity and tethering in failing myocytes. Therapeutically targeting BL remodeling could slow or prevent the progression of heart disease.
Authors: Leanne Elizabeth Felkin; Enrique A Lara-Pezzi; Jennifer L Hall; Emma J Birks; Paul J R Barton Journal: J Cardiovasc Transl Res Date: 2011-03-22 Impact factor: 4.132
Authors: Manuel Mayr; Jun Zhang; Andrew S Greene; David Gutterman; Joseph Perloff; Peipei Ping Journal: Mol Cell Proteomics Date: 2006-05-29 Impact factor: 5.911
Authors: M Cotrufo; L De Santo; A Della Corte; F Di Meglio; G Guerra; C Quarto; S Vitale; C Castaldo; S Montagnani Journal: Eur J Histochem Date: 2005 Oct-Dec Impact factor: 3.188
Authors: Boris Z Simkhovich; Paul Marjoram; Coralie Poizat; Larry Kedes; Robert A Kloner Journal: Arch Biochem Biophys Date: 2003-12-15 Impact factor: 4.013
Authors: Heiko Bugger; Michael Schwarzer; Dong Chen; Andrea Schrepper; Paulo A Amorim; Maria Schoepe; T Dung Nguyen; Friedrich W Mohr; Oleh Khalimonchuk; Bart C Weimer; Torsten Doenst Journal: Cardiovasc Res Date: 2009-10-19 Impact factor: 10.787
Authors: Ayla O Sessions; Gaurav Kaushik; Sarah Parker; Koen Raedschelders; Rolf Bodmer; Jennifer E Van Eyk; Adam J Engler Journal: Matrix Biol Date: 2016-10-25 Impact factor: 11.583
Authors: Sarah E Lang; Tamara K Stevenson; Tabea M Schatz; Brandon J Biesiadecki; Margaret V Westfall Journal: Arch Biochem Biophys Date: 2017-06-03 Impact factor: 4.013
Authors: Yimu Zhao; Amandine Godier-Furnemont; Noortje A M Bax; Carlijn V C Bouten; Lewis M Brown; Barry Fine; Gordana Vunjak-Novakovic Journal: J Mol Cell Cardiol Date: 2022-02-24 Impact factor: 5.763
Authors: Hadi R Ali; Cole R Michel; Ying H Lin; Timothy A McKinsey; Mark Y Jeong; Amrut V Ambardekar; Joseph C Cleveland; Richard Reisdorph; Nichole Reisdorph; Kathleen C Woulfe; Kristofer S Fritz Journal: J Mol Cell Cardiol Date: 2019-12-10 Impact factor: 5.000