BACKGROUND: Left ventricular assist device (LVAD) support is commonly used in patients with heart failure as a bridge to heart transplantation. Whereas myocardial gene expression profile changes have been well established after LVAD support, the consequences on the protein level largely remain unclear. METHODS: Pre-LVAD and post-LVAD myocardial tissue specimens from dilated cardiomyopathy (DCM) and ischemic heart disease (IHD) patients were analyzed by fluorescent 2-dimensional difference gel electrophoresis, and differentially expressed proteins were identified by mass spectrometry. RESULTS: In the DCM group, 16 proteins were detected that showed statistically significant downregulation from pre-LVAD to post-LVAD tissue. In IHD patients, 50 alterations were found, including upregulated (n = 12) and downregulated (n = 38) proteins. The identified proteins in both groups partially overlapped and included proteins from cytoskeleton and mitochondrial energy metabolism. The latter changes were paralleled by severe abnormalities in mitochondrial morphology, as shown by electron microscopy. Post-LVAD proteomes of both DCM and IHD patients largely mimicked the protein profiles of non-failing hearts. Downregulation of the serine protease inhibitor α-1-antichymotrypsin in both DCM and IHD patients after LVAD support was confirmed by immunosorbent assay. CONCLUSIONS: LVAD-induced cardiac remodeling in DCM and IHD patients is associated with downregulation of α-1-antichymotrypsin and specific atrophic changes in protein expression profiles predominantly involved in cytoskeleton integrity and mitochondrial energy metabolism.
BACKGROUND: Left ventricular assist device (LVAD) support is commonly used in patients with heart failure as a bridge to heart transplantation. Whereas myocardial gene expression profile changes have been well established after LVAD support, the consequences on the protein level largely remain unclear. METHODS: Pre-LVAD and post-LVAD myocardial tissue specimens from dilated cardiomyopathy (DCM) and ischemic heart disease (IHD) patients were analyzed by fluorescent 2-dimensional difference gel electrophoresis, and differentially expressed proteins were identified by mass spectrometry. RESULTS: In the DCM group, 16 proteins were detected that showed statistically significant downregulation from pre-LVAD to post-LVAD tissue. In IHD patients, 50 alterations were found, including upregulated (n = 12) and downregulated (n = 38) proteins. The identified proteins in both groups partially overlapped and included proteins from cytoskeleton and mitochondrial energy metabolism. The latter changes were paralleled by severe abnormalities in mitochondrial morphology, as shown by electron microscopy. Post-LVAD proteomes of both DCM and IHD patients largely mimicked the protein profiles of non-failing hearts. Downregulation of the serine protease inhibitor α-1-antichymotrypsin in both DCM and IHD patients after LVAD support was confirmed by immunosorbent assay. CONCLUSIONS:LVAD-induced cardiac remodeling in DCM and IHD patients is associated with downregulation of α-1-antichymotrypsin and specific atrophic changes in protein expression profiles predominantly involved in cytoskeleton integrity and mitochondrial energy metabolism.
Authors: Stavros G Drakos; Abdallah G Kfoury; Josef Stehlik; Craig H Selzman; Bruce B Reid; John V Terrovitis; John N Nanas; Dean Y Li Journal: Circulation Date: 2012-07-10 Impact factor: 29.690
Authors: Daniel J Sassoon; Adam G Goodwill; Jillian N Noblet; Abass M Conteh; B Paul Herring; Jeanette N McClintick; Johnathan D Tune; Kieren J Mather Journal: Basic Res Cardiol Date: 2016-05-27 Impact factor: 17.165
Authors: Helen E Collins; Mariame Selma Kane; Silvio H Litovsky; Victor M Darley-Usmar; Martin E Young; John C Chatham; Jianhua Zhang Journal: Front Aging Date: 2021-05-06
Authors: Anisha A Gupte; Dale J Hamilton; Andrea M Cordero-Reyes; Keith A Youker; Zheng Yin; Jerry D Estep; Robert D Stevens; Brett Wenner; Olga Ilkayeva; Matthias Loebe; Leif E Peterson; Christopher J Lyon; Stephen T C Wong; Christopher B Newgard; Guillermo Torre-Amione; Heinrich Taegtmeyer; Willa A Hsueh Journal: Circ Cardiovasc Genet Date: 2014-05-13
Authors: Esther Roselló-Lletí; Estefanía Tarazón; María G Barderas; Ana Ortega; Manuel Otero; Maria Micaela Molina-Navarro; Francisca Lago; Jose Ramón González-Juanatey; Antonio Salvador; Manuel Portolés; Miguel Rivera Journal: PLoS One Date: 2014-11-14 Impact factor: 3.240
Authors: Shiraj Sen; Bijoy K Kundu; Henry Cheng-Ju Wu; S Shahrukh Hashmi; Patrick Guthrie; Landon W Locke; R Jack Roy; G Paul Matherne; Stuart S Berr; Matthew Terwelp; Brian Scott; Sylvia Carranza; O Howard Frazier; David K Glover; Wolfgang H Dillmann; Michael J Gambello; Mark L Entman; Heinrich Taegtmeyer Journal: J Am Heart Assoc Date: 2013-05-17 Impact factor: 5.501