title: Chronomics of pressure overload-induced cardiac hypertrophy in mice reveals altered day/night gene expression and biomarkers of heart disease.
abstract: There is critical demand in contemporary medicine for gene expression markers in all areas of human disease, for early detection of disease, classification, prognosis, and response to therapy. The integrity of circadian gene expression underlies cardiovascular health and disease; however time-of-day profiling in heart disease has never been examined. We hypothesized that a time-of-day chronomic approach using samples collected across 24-h cycles and analyzed by microarrays and bioinformatics advances contemporary approaches, because it includes sleep-time and/or wake-time molecular responses. As proof of concept, we demonstrate the value of this approach in cardiovascular disease using a murine Transverse Aortic Constriction (TAC) model of pressure overload-induced cardiac hypertrophy in mice. First, microarrays and a novel algorithm termed DeltaGene were used to identify time-of-day differences in gene expression in cardiac hypertrophy 8 wks post-TAC. The top 300 candidates were further analyzed using knowledge-based platforms, paring the list to 20 candidates, which were then validated by real-time polymerase chain reaction (RTPCR). Next, we tested whether the time-of-day gene expression profiles could be indicative of disease progression by comparing the 1- vs. 8-wk TAC. Lastly, since protein expression is functionally relevant, we monitored time-of-day cycling for the analogous cardiac proteins. This approach is generally applicable and can lead to new understanding of disease.
authors: Cardiovascular Research Group, Department of Biomedical Sciences, University of Guelph, Guelph, Ontario, Canada.
authors: Elena V
authors: EV
authors: Tsimakouridze
authors: Marty
authors: M
authors: Straume
authors: Peter S
authors: PS
authors: Podobed
authors: Heather
authors: H
authors: Chin
authors: Jonathan
authors: J
authors: LaMarre
authors: Ron
authors: R
authors: Johnson
authors: Monica
authors: M
authors: Antenos
authors: Gordon M
authors: GM
authors: Kirby
authors: Allison
authors: A
authors: Mackay
authors: Patsy
authors: P
authors: Huether
authors: Jeremy A
authors: JA
authors: Simpson
authors: Michael
authors: M
authors: Sole
authors: Gerard
authors: G
authors: Gadal
authors: Tami A
authors: TA
authors: Martino
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001794:Blood Pressure; D006332:Cardiomegaly / Q000209:etiology / Q000235:genetics* / Q000503:physiopathology*; D002940:Circadian Rhythm / Q000235:genetics*; D004195:Disease Models, Animal; D018450:Disease Progression; D006801:Humans; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism; D016547:Kinesins / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D040081:Protein Array Analysis; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics / Q000378:metabolism; D059467:Transcriptome; D000071247:Uncoupling Protein 3; D020257:Ventricular Remodeling
chemical_list: D015415:Biomarkers; D007473:Ion Channels; D024101:Mitochondrial Proteins; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D012333:RNA, Messenger; D000071247:Uncoupling Protein 3; D019716:Tissue Inhibitor of Metalloproteinase-2; D017346:Protein Serine-Threonine Kinases; C475469:Kif5b protein, mouse; D016547:Kinesins