Integrated genomic approaches implicate osteoglycin (Ogn) in the regulation of left ventricular mass.
Left ventricular mass (LVM) and cardiac gene expression are complex traits regulated by factors both intrinsic and extrinsic to the heart. To dissect the major determinants of LVM, we combined expression quantitative trait locus1 and quantitative trait transcript (QTT) analyses of the cardiac transcriptome in the rat. Using these methods and in vitro functional assays, we identified osteoglycin (Ogn) as a major candidate regulator of rat LVM, with increased Ogn protein expression associated with elevated LVM. We also applied genome-wide QTT analysis to the human heart and observed that, out of 22,000 transcripts, OGN transcript abundance had the highest correlation with LVM. We further confirmed a role for Ogn in the in vivo regulation of LVM in Ogn knockout mice. Taken together, these data implicate Ogn as a key regulator of LVM in rats, mice and humans, and suggest that Ogn modifies the hypertrophic response to extrinsic factors such as hypertension and aortic stenosis.
Petretto
Enrico
E
Medical Research Council Clinical Sciences Centre, Faculty of Medicine, Imperial College London, Hammersmith Hospital, Du Cane Road, London, W12 0NN, UK.
Sarwar
Rizwan
R
Grieve
Ian
I
Lu
Han
H
Kumaran
Mande K
MK
Muckett
Phillip J
PJ
Mangion
Jonathan
J
Schroen
Blanche
B
Benson
Matthew
M
Punjabi
Prakash P
PP
Prasad
Sanjay K
SK
Pennell
Dudley J
DJ
Kiesewetter
Chris
C
Tasheva
Elena S
ES
Corpuz
Lolita M
LM
Webb
Megan D
MD
Conrad
Gary W
GW
Kurtz
Theodore W
TW
Kren
Vladimir
V
Fischer
Judith
J
Hubner
Norbert
N
Pinto
Yigal M
YM
Pravenec
Michal
M
Aitman
Timothy J
TJ
Cook
Stuart A
SA
D000818:Animals; D001024:Aortic Valve Stenosis / Q000150:complications / Q000235:genetics; D001794:Blood Pressure / Q000235:genetics; D002874:Chromosome Mapping; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D023281:Genomics; D006023:Glycoproteins / Q000235:genetics / Q000502:physiology*; D006352:Heart Ventricles / Q000033:anatomy & histology* / Q000378:metabolism; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000235:genetics; D017379:Hypertrophy, Left Ventricular / Q000235:genetics*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009929:Organ Size / Q000235:genetics; D040641:Quantitative Trait Loci; D051381:Rats / Q000235:genetics*; D011922:Rats, Mutant Strains
D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; C063488:OGN protein, human; C512906:Ogn protein, mouse; C512905:Ogn protein, rat