Maintaining PGC-1a expression following pressure overload-induced cardiac
hypertrophy preserves angiogenesis but not contractile or mitochondrial
function.
Authors Pereira RO, Wende AR, Crum A, Hunter D, Olsen CD, Rawlings T, Riehle C, Ward WF,
Abel ED
Submitted By Adam Wende on 3/4/2015
Status Published
Journal FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Year 2014
Date Published 8/1/2014
Volume : Pages 28 : 3691 - 702
PubMed Reference 24776744
Abstract During pathological hypertrophy, peroxisome proliferator-activated receptor
coactivator 1a (PGC-1a) is repressed in concert with reduced mitochondrial
oxidative capacity and fatty acid oxidation (FAO). We therefore sought to
determine if maintaining or increasing PGC-1a levels in the context of pressure
overload hypertrophy (POH) would preserve mitochondrial function and prevent
contractile dysfunction. Pathological cardiac hypertrophy was induced using 4 wk
of transverse aortic constriction (TAC) in mice overexpressing the human PGC-1a
genomic locus via a bacterial artificial chromosome (TG) and nontransgenic
controls (Cont). PGC-1a levels were increased by 40% in TG mice and were
sustained following TAC. Although TAC-induced repression of FAO genes and
oxidative phosphorylation (oxphos) genes was prevented in TG mice, mitochondrial
function and ATP synthesis were equivalently impaired in Cont and TG mice after
TAC. Contractile function was also equally impaired in Cont and TG mice
following TAC, as demonstrated by decreased +dP/dt and ejection fraction and
increased left ventricular developed pressure and end diastolic pressure.
Conversely, capillary density was preserved, in concert with increased VEGF
expression, while apoptosis and fibrosis were reduced in TG relative to Cont
mice after TAC. Hence, sustaining physiological levels of PGC-1a expression
following POH, while preserving myocardial vascularity, does not prevent
mitochondrial and contractile dysfunction.


Investigators with authorship
NameInstitution
E. Dale AbelUniversity of Iowa
Adam WendeUniversity of Alabama at Birmingham

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