Open AccessComparative differential proteomic profiles of nonfailing and failing hearts after in vivo thoracic aortic constriction in mice overexpressing FKBP 12.6
Author(s) -
Prévilon Miresta,
Gall Morgane,
Chafey Philippe,
Federeci Christian,
Pezet Mylène,
Clary Guilhem,
Broussard Cédric,
François Guillonneau,
Mercadier JeanJacques,
RouetBenzineb Patricia
Publication year - 2013
Publication title -
physiological reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 39
ISSN - 2051-817X
DOI - 10.1002/phy2.39
Subject(s) - heart failure , pressure overload , medicine , endocrinology , muscle hypertrophy , ventricular remodeling , biology , cardiac hypertrophy
Chronic pressure overload ( PO ) induces pathological left ventricular hypertrophy ( LVH ) leading to congestive heart failure ( HF ). Overexpression of FKBP 12.6 ( FK 506‐binding protein [K]) in mice should prevent Ca2+‐leak during diastole and may improve overall cardiac function. In order to decipher molecular mechanisms involved in thoracic aortic constriction ( TAC )‐induced cardiac remodeling and the influence of gender and genotype, we performed a proteomic analysis using two‐dimensional differential in‐gel electrophoresis (2D‐ DIGE ), mass spectrometry, and bioinformatics techniques to identify alterations in characteristic biological networks. Wild‐type (W) and K mice of both genders underwent TAC . Thirty days post‐ TAC , the altered cardiac remodeling was accompanied with systolic and diastolic dysfunction in all experimental groups. A gender difference in inflammatory protein expression (fibrinogen, α‐1‐antitrypsin isoforms) and in calreticulin occurred (males > females). Detoxification enzymes and cytoskeletal proteins were noticeably increased in K mice. Both non‐ and congestive failing mouse heart exhibited down‐ and upregulation of proteins related to mitochondrial function and purine metabolism, respectively. HF was characterized by a decrease in enzymes related to iron homeostasis, and altered mitochondrial protein expression related to fatty acid metabolism, glycolysis, and redox balance. Moreover, two distinct differential protein profiles characterized TAC ‐induced pathological LVH and congestive HF in all TAC mice. FKBP 12.6 overexpression did not influence TAC ‐induced deleterious effects. Huntingtin was revealed as a potential mediator for HF . A broad dysregulation of signaling proteins associated with congestive HF suggested that different sets of proteins could be selected as useful biomarkers for HF progression and might predict outcome in PO ‐induced pathological LVH .