Transcriptional Regulation of the Fetal Cardiac Gene Program

Kuwahara, Koichiro; Nishikimi, Toshio; Nakao, Kazuwa

doi:10.1254/jphs.12r04cp

Cited by 88 publications

(62 citation statements)

References 52 publications

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“…The immature myocardium is generally known to have electrophysiological and contractile properties different from those of the adult myocardium (2,5,6). In the case of the mouse heart, the beating rate increases during pre-and postnatal development; the heart rate of the fetal mouse reaches 200 on the 16th fetal day (7), is about 320 on the day of birth, and reaches the adult level of about 700 at 2 weeks after birth (1,8).…”

Section: Introductionmentioning

confidence: 99%

Developmental Changes in Excitation–Contraction Mechanisms of the Mouse Ventricular Myocardium as Revealed by Functional and Confocal Imaging Analyses

et al. 2013

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Abstract. Developmental changes in excitation-contraction mechanisms were examined in the ventricular myocardium from fetal, neonatal, and 1-, 2-, and 4-week-old mice. In isolated tissue, the negative inotropic effect of nifedipine decreased, while that of ryanodine increased with age. Action potential duration decreased with age, especially during the late fetal period. In ventricular cardiomyocytes, fluorescence imaging revealed that the sarcoplasmic reticulum increases progressively during pre-and postnatal development. t-Tubules were absent in the fetus and neonate, were observed only in the subsarcolemmal region at 1 week after birth, and were present throughout the cytoplasm at 2 and 4 weeks after birth. The amplitude of Ca 2+ transients, as well as its ryanodine-sensitive component, increased with age. In the neonate and 1-week-old mice, Ca 2+ at the cell center showed slower rise than the subsarcolemmal region, but in 2-and 4-week-old mice, Ca 2+ increased simultaneously across the entire width of the cell. These results suggest that in the mouse ventricular myocardium, the shortening of the action potential during the late fetal period and the development of t-tubule-sarcoplasmic reticulum coupling during the second postnatal week largely contribute to the developmental increase in the dependence of contraction on sarcoplasmic reticulum function.

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Section: Introductionmentioning

confidence: 99%

Developmental Changes in Excitation–Contraction Mechanisms of the Mouse Ventricular Myocardium as Revealed by Functional and Confocal Imaging Analyses

et al. 2013

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“…We investigated whether changes in these transcription factor interactions were associated with changes in the expression of fetal genes, such as ANP, BNP, and skeletal α-actin, which are regulated by REST and mSin3A [20,53]. Transcript levels of ANP and β-myosin heavy chain were not different between groups, but BNP and skeletal α-actin were significantly reduced in db hearts independent of exercise (Figure 10).…”

Section: Resultsmentioning

confidence: 99%

“…Similarly, lowering O-GlcNAc by intensive swim training [43,44] has been proposed as a mechanism by which exercise benefits the diabetic heart, and exercise lowers both the O-GlcNAc modification of the SP1 transcription factor and the OGT enzyme. O-GlcNAc directly mediates the expression of fetal genes in response to hypertrophic stimuli [29], and O-GlcNAc modifies mSin3A and HDAC1 [35], which regulate cardiac hypertrophy [20,58]. Previously, we have shown that exercise lowers the O-GlcNAc modification of the OGT enzyme [32], and others have shown that exercise lowers O-GlcNAcylation of the SP1 transcription factor [43].…”

Section: Discussionmentioning

confidence: 99%

Exercise and diabetes have opposite effects on the assembly and O-GlcNAc modification of the mSin3A/HDAC1/2 complex in the heart

Cox

Marsh

2013

Cardiovasc Diabetol

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BackgroundExercise causes physiological cardiac hypertrophy and benefits the diabetic heart. Mammalian switch-independent 3A (mSin3A) and histone deacetylases (HDACs) 1 and 2 regulate hypertrophic genes through associations with the DNA binding proteins repressor element-1 silencing transcription factor (REST) and O-linked β-N-acetylglucosamine transferase (OGT). O-linked β-N-acetylglucosamine (O-GlcNAc) is a glucose derivative that is chronically elevated in diabetic hearts, and a previous study showed that exercise reduces cardiac O-GlcNAc. We hypothesized that O-GlcNAc and OGT would physically associate with mSin3A/HDAC1/2 in the heart, and that this interaction would be altered by diabetes and exercise.Methods8-week-old type 2 diabetic db/db (db) and non-diabetic C57 mice were randomized to treadmill exercise or sedentary groups for 1 or 4 weeks.ResultsO-GlcNAc was significantly higher in db hearts and increased with exercise. Db hearts showed lower levels of mSin3A, HDAC1, and HDAC2 protein, but higher levels of HDAC2 mRNA and HDAC1/2 deacetylase activity. Elevated HDAC activity was associated with significantly blunted expression of α-actin and brain natriuretic peptide in db hearts. In sedentary db hearts, co-immunoprecipitation assays showed that mSin3A and OGT were less associated with HDAC1 and HDAC2, respectively, compared to sedentary C57 controls; however, exercise removed these differences.ConclusionsThese data indicate that diabetes and exercise oppositely affect interactions between pro-hypertrophic transcription factors, and suggest that an increase in total cardiac O-GlcNAc is a mechanism by which exercise benefits type 2 diabetic hearts.

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“…Under normal conditions the adult heart generates 70% of its ATP through fatty acid oxidation and 30% through glucose and lactate metabolism [8]. Heart failure is not only characterized by modified ventricular mass, but also by a switch to the fetal gene expression program causing altered substrate utilization [9]. The fetal heart develops in an environment low in oxygen that preferentially uses glucose as a substrate for energy [10, 11].…”

Section: Introductionmentioning

confidence: 99%

A High Fat Diet During Pregnancy and Lactation Induces Cardiac and Renal Abnormalities in GLUT4 +/- Male Mice

Kruse¹,

Fiallo²,

Jiang³

et al. 2017

Kidney Blood Press Res

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Background/Aims: Altered nutrients during the in utero (IU) and/or lactation (L) period predispose offspring to cardio-renal diseases in adulthood. This study investigates the effect of a high fat diet (HFD) fed to female mice during IU/L on gene expression patterns associated with heart and kidney failure and hypertension in male offspring. Methods: Female wild type (WT) mice were fed either a HFD or control chow (C) prior to mating with males with a genetic heterozygous deletion of GLUT4 (G4+/-, a model of peripheral insulin resistance and hypertension) and throughout IU/L. After weaning male offspring were placed on a standard rodent chow until 24 weeks of age. Results: All offspring exposed to a maternal HFD showed increased heart and kidney weight and reduced cardiac insulin responsiveness. G4+/- offspring on a HFD displayed early hypertension associated with increased renal gene expression of renin and the AT₁- receptors compared to G4+/- on a C diet. This group showed decreased cardiac expression of key genes involved in fatty acid oxidation compared to WT on a C diet. Conclusions: These results indicate an interaction between a HFD diet and genotype during early life development that can enhance susceptibility to cardio-renal diseases later in life.

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Transcriptional Regulation of the Fetal Cardiac Gene Program

Cited by 88 publications

References 52 publications

Developmental Changes in Excitation–Contraction Mechanisms of the Mouse Ventricular Myocardium as Revealed by Functional and Confocal Imaging Analyses

Developmental Changes in Excitation–Contraction Mechanisms of the Mouse Ventricular Myocardium as Revealed by Functional and Confocal Imaging Analyses

Exercise and diabetes have opposite effects on the assembly and O-GlcNAc modification of the mSin3A/HDAC1/2 complex in the heart

A High Fat Diet During Pregnancy and Lactation Induces Cardiac and Renal Abnormalities in GLUT4 +/- Male Mice

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