Transcription of early developmental isogenes in cardiac myocyte hypertrophy

Simpson, Paul C.; Long, Carlin S.; Waspe, Lawrence E.; Henrich, Curtis J.; Ordahl, Charles P.

doi:10.1016/0022-2828(89)90774-8

Cited by 79 publications

(33 citation statements)

References 50 publications

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“…Pressure overload and other pathological stresses typically cause induction of the fetal hypertrophic gene program, which is correlated with pathological ventricular remodeling (28). In WT hearts, as expected, TAC robustly increased the mRNA levels of the fetal genes atrial natriuretic factor (ANF), β-myosin heavy chain (βMyHC), and α-skeletal actin (SkAct; Figure 4 and Table 1).…”

Section: Figuresupporting

confidence: 57%

1-Adrenergic receptors prevent a maladaptive cardiac response to pressure overload

OʼConnell

Swigart²,

Rodrigo

et al. 2006

Journal of Clinical Investigation

130

139

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An α 1 -adrenergic receptor (α 1 -AR) antagonist increased heart failure in the Antihypertensive and LipidLowering Treatment to Prevent Heart Attack Trial (ALLHAT), but it is unknown whether this adverse result was due to α 1 -AR inhibition or a nonspecific drug effect. We studied cardiac pressure overload in mice with double KO of the 2 main α 1 -AR subtypes in the heart, α 1A (Adra1a) and α 1B (Adra1b). At 2 weeks after transverse aortic constriction (TAC), KO mouse survival was only 60% of WT, and surviving KO mice had lower ejection fractions and larger end-diastolic volumes than WT mice. Mechanistically, final heart weight and myocyte cross-sectional area were the same after TAC in KO and WT mice. However, KO hearts after TAC had increased interstitial fibrosis, increased apoptosis, and failed induction of the fetal hypertrophic genes. Before TAC, isolated KO myocytes were more susceptible to apoptosis after oxidative and β-AR stimulation, and β-ARs were desensitized. Thus, α 1 -AR deletion worsens dilated cardiomyopathy after pressure overload, by multiple mechanisms, indicating that α 1 -signaling is required for cardiac adaptation. These results suggest that the adverse cardiac effects of α 1 -antagonists in clinical trials are due to loss of α 1 -signaling in myocytes, emphasizing concern about clinical use of α 1 -antagonists, and point to a revised perspective on sympathetic activation in heart failure.

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Section: Figuresupporting

confidence: 57%

1-Adrenergic receptors prevent a maladaptive cardiac response to pressure overload

OʼConnell

Swigart²,

Rodrigo

et al. 2006

Journal of Clinical Investigation

130

139

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“…7,8 An intriguing observation is that pathological hypertrophy is characterized by hypothyroid-like changes in these target genes, with decreases in ␣-MyHC and SERCA and increases in ␤-MyHC, a molecular phenotype also called the fetal program. 9 The fact that TH treatment can reverse these genetic changes in some models of pathological hypertrophy is additional evidence for a hypothyroid state, but TH blood levels are usually normal. 3 Conversely, physiological hypertrophy caused by exercise is characterized by hyperthyroid-like changes in TH target genes, yet again blood TH levels are normal.…”

mentioning

confidence: 99%

Regulation of Thyroid Hormone Receptor Isoforms in Physiological and Pathological Cardiac Hypertrophy

Kinugawa

Yonekura

Ribeiro

et al. 2001

Circulation Research

181

123

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Abstract-Physiological and pathological cardiac hypertrophy have directionally opposite changes in transcription of thyroid hormone (TH)-responsive genes, including ␣-and ␤-myosin heavy chain (MyHC) and sarcoplasmic reticulum Ca 2ϩ -ATPase (SERCA), and TH treatment can reverse molecular and functional abnormalities in pathological hypertrophy, such as pressure overload. These findings suggest relative hypothyroidism in pathological hypertrophy, but serum levels of TH are usually normal. We studied the regulation of TH receptors (TRs) ␤1, ␣1, and ␣2 in pathological and physiological rat cardiac hypertrophy models with hypothyroid-and hyperthyroid-like changes in the TH target genes, ␣-and ␤-MyHC and SERCA. All 3 TR subtypes in myocytes were downregulated in 2 hypertrophy models with a hypothyroid-like mRNA phenotype, phenylephrine in culture and pressure overload in vivo. Myocyte TR␤1 was upregulated in models with a hyperthyroid-like phenotype, TH (triiodothyronine, T3), in culture and exercise in vivo. In myocyte culture, TR overexpression, or excess T3, reversed the effects of phenylephrine on TH-responsive mRNAs and promoters. In addition, TR cotransfection and treatment with the TR␤1-selective agonist GC-1 suggested different functional coupling of the TR isoforms, TR␤1 to transcription of ␤-MyHC, SERCA, and TR␤1, and TR␣1 to ␣-MyHC transcription and increased myocyte size. We conclude that TR isoforms have distinct regulation and function in rat cardiac myocytes. Changes in myocyte TR levels can explain in part the characteristic molecular phenotypes in physiological and pathological cardiac hypertrophy. (Circ Res. 2001;89:591-598.) Key Words: thyroid hormone receptor Ⅲ physiological and pathological hypertrophy Ⅲ ␣ 1 -adrenergic receptor Ⅲ cardiac myocyte Ⅲ rat C ardiac hypertrophy is sometimes considered a single process that leads invariably to myocardial dysfunction (pathological hypertrophy). However, physiological hypertrophy exists in which cardiac function is maintained or enhanced, including normal cardiac development, exercise training, and thyroid hormone (TH) treatment. Exercise and TH can reverse molecular and functional abnormalities in pathological hypertrophy without decreasing ventricular mass, indicating that physiological and pathological hypertrophy are qualitatively distinct processes. [1][2][3][4][5][6] TH-responsive genes in cardiac muscle include ␣-myosin heavy chain (MyHC) and sarcoplasmic reticulum Ca 2ϩ -ATPase (SERCA), which are induced by TH, and ␤-MyHC, which is repressed. 7,8 An intriguing observation is that pathological hypertrophy is characterized by hypothyroid-like changes in these target genes, with decreases in ␣-MyHC and SERCA and increases in ␤-MyHC, a molecular phenotype also called the fetal program. 9 The fact that TH treatment can reverse these genetic changes in some models of pathological hypertrophy is additional evidence for a hypothyroid state, but TH blood levels are usually normal. 3 Conversely, physiological hypertrophy caused by exercise is characterized ...

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“…Changes in ventricular structure, function, and gene expression have been described in patients with heart failure (22,35) and animal models of myocardial infarction (8,47). Similar abnormalities in gene expression have been induced in myocardial cell cultures (2,33).…”

mentioning

confidence: 78%

Prolonged administration of a dithiol antioxidant protects against ventricular remodeling due to ischemia-reperfusion in mice

Ambler¹,

Hodges²,

Jones³

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

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Ambler SK, Hodges YK, Jones GM, Long CS, Horwitz LD. Prolonged administration of a dithiol antioxidant protects against ventricular remodeling due to ischemia-reperfusion in mice. Am J Physiol Heart Circ Physiol 295: H1303-H1310, 2008. doi:10.1152/ajpheart.01143.2007.-The prolonged production of reactive oxygen species due to ischemiareperfusion (I/R) is a potential cause of the pathological remodeling that frequently precedes heart failure. We tested the ability of a potent dithiol antioxidant, bucillamine, to protect against the long-term consequences of I/R injury in a murine model of myocardial infarction. After transiently occluding the left anterior descending coronary artery for 30 min, saline or bucillamine (10 g/g body wt) was injected intravenously as a bolus within the first 5 min of reperfusion. The antioxidant treatment continued with daily subcutaneous injections for 4 wk. There were no differences in infarct sizes between bucillamine-and saline-treated animals. After 4 wk of reperfusion, cardiac hypertrophy was decreased by bucillamine treatment (ventricular weight-to-body weight ratios: I/R ϩ saline, 4.5 Ϯ 0.2 mg/g vs.

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Transcription of early developmental isogenes in cardiac myocyte hypertrophy

Cited by 79 publications

References 50 publications

1-Adrenergic receptors prevent a maladaptive cardiac response to pressure overload

1-Adrenergic receptors prevent a maladaptive cardiac response to pressure overload

Regulation of Thyroid Hormone Receptor Isoforms in Physiological and Pathological Cardiac Hypertrophy

Prolonged administration of a dithiol antioxidant protects against ventricular remodeling due to ischemia-reperfusion in mice

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