Time course of the in vivo effects of thyroid hormone on cardiac gene expression

Endocrinology ◽  
1992 ◽  
Vol 130 (4) ◽  
pp. 2001-2006 ◽  
Author(s):  
C. Balkman
Keyword(s):  
Gene Expression ◽  
Thyroid Hormone ◽  
Time Course ◽  
Cardiac Gene Expression ◽  
Cardiac Gene ◽  
In Vivo Effects

Multifactorial Regulation of Cardiac Gene Expression: an In Vivo and In Vitro Analysis

1995 ◽  
Vol 752 (1 Cardiac Growt) ◽  
pp. 370-386 ◽  
Author(s):  
J. L. SAMUEL ◽  
I. DUBUS ◽  
F. FARHADIAN ◽  
F. MAROTTE ◽  
P. OLIVIERO ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cardiac Gene Expression ◽  
Cardiac Gene ◽  
Vitro Analysis ◽  
In Vitro Analysis

Adrenergic induction of bimodal myocardial protection: signal transduction and cardiac gene reprogramming

1999 ◽  
Vol 276 (5) ◽  
pp. R1525-R1533 ◽  
Author(s):  
Xianzhong Meng ◽  
Brian D. Shames ◽  
Edward J. Pulido ◽  
Daniel R. Meldrum ◽  
Lihua Ao ◽  
...  
Keyword(s):  
Gene Expression ◽  
Signal Transduction ◽  
Adaptive Response ◽  
Ischemia Reperfusion ◽  
Functional Adaptation ◽  
Immunofluorescent Staining ◽  
Northern Analysis ◽  
Cardiac Gene Expression ◽  
Cardiac Gene

This study tested the hypothesis that in vivo norepinephrine (NE) treatment induces bimodal cardiac functional protection against ischemia and examined the roles of α1-adrenoceptors, protein kinase C (PKC), and cardiac gene expression in cardiac protection. Rats were treated with NE (25 μg/kg iv). Cardiac functional resistance to ischemia-reperfusion (25/40 min) injury was examined 30 min and 1, 4, and 24 h after NE treatment with the Langendorff technique, and effects of α1-adrenoceptor antagonism and PKC inhibition on the protection were determined. Northern analysis was performed to examine cardiac expression of mRNAs encoding α-actin and myosin heavy chain (MHC) isoforms. Immunofluorescent staining was performed to localize PKC-βI in the ventricular myocardium. NE treatment improved postischemic functional recovery at 30 min, 4 h, and 24 h but not at 1 h. Pretreatment with prazosin or chelerythrine abolished both the early adaptive response at 30 min and the delayed adaptive response at 24 h. NE treatment induced intranuclear translocation of PKC-βI in cardiac myocytes at 10 min and increased skeletal α-actin and β-MHC mRNAs in the myocardium at 4–24 h. These results demonstrate that in vivo NE treatment induces bimodal myocardial functional adaptation to ischemia in a rat model. α1-Adrenoceptors and PKC appear to be involved in signal transduction for inducing both the early and delayed adaptive responses. The delayed adaptive response is associated with the expression of cardiac genes encoding fetal contractile proteins, and PKC-βI may transduce the signal for reprogramming of cardiac gene expression.

scholarly journals Impaired sarcoplasmic reticulum function leads to contractile dysfunction and cardiac hypertrophy

2001 ◽  
Vol 280 (5) ◽  
pp. H2046-H2052 ◽  
Author(s):  
Markus Meyer ◽  
Susanne U. Trost ◽  
Wolfgang F. Bluhm ◽  
Harm J. Knot ◽  
Eric Swanson ◽  
...  
Keyword(s):  
Gene Expression ◽  
Sarcoplasmic Reticulum ◽  
Cardiac Hypertrophy ◽  
Late Phase ◽  
Cardiac Contractility ◽  
Maximum Speed ◽  
Cardiac Gene Expression ◽  
Cardiac Gene ◽  
End Stage

Sarcoplasmic reticulum (SR)-mediated Ca2+ sequestration and release are important determinants of cardiac contractility. In end-stage heart failure SR dysfunction has been proposed to contribute to the impaired cardiac performance. In this study we tested the hypothesis that a targeted interference with SR function can be a primary cause of contractile impairment that in turn might alter cardiac gene expression and induce cardiac hypertrophy. To study this we developed a novel animal model in which ryanodine, a substance that alters SR Ca2+ release, was added to the drinking water of mice. After 1 wk of treatment, in vivo hemodynamic measurements showed a 28% reduction in the maximum speed of contraction (+dP/d t max) and a 24% reduction in the maximum speed of relaxation (−dP/d t max). The slowing of cardiac relaxation was confirmed in isolated papillary muscles. The late phase of relaxation expressed as the time from 50% to 90% relaxation was prolonged by 22%. After 4 wk of ryanodine administration the animals had developed a significant cardiac hypertrophy that was most prominent in both atria (right artrium +115%, left atrium +100%, right ventricle +23%, and left ventricle +13%). This was accompanied by molecular changes including a threefold increase in atrial natriuretic factor mRNA and a sixfold increase in β-myosin heavy chain mRNA. Sarcoplasmic endoplasmic reticulum Ca2+ mRNA was reduced by 18%. These data suggest that selective impairment of SR function in vivo can induce changes in cardiac gene expression and promote cardiac growth.

Sp3 inhibits Sp1-mediated activation of the cardiac troponin T promoter and is downregulated during pathological cardiac hypertrophy in vivo

2006 ◽  
Vol 291 (2) ◽  
pp. H600-H611 ◽  
Author(s):  
Anthony Azakie ◽  
Jeffrey R. Fineman ◽  
Youping He
Keyword(s):  
Gene Expression ◽  
Cardiac Hypertrophy ◽  
Cardiac Troponin ◽  
Troponin T ◽  
Cardiac Troponin T ◽  
Pathological Cardiac Hypertrophy ◽  
Cardiac Gene Expression ◽  
Cardiac Gene ◽  
Embryonic Cardiomyocytes

Combinatorial interactions between cis elements and trans-acting factors are required for regulation of cardiac gene expression during normal cardiac development and pathological cardiac hypertrophy. Sp factors bind GC boxes and are implicated in recruitment and assembly of the basal transcriptional complex. In this study, we show that the cardiac troponin T (cTnT) promoter contains a GC box that is necessary for basal and cAMP-mediated activity of cTnT promoter constructs transfected in embryonic cardiomyocytes. Cardiac nuclear proteins bind the cTnT GC box in a sequence-specific fashion and consist of Sp1, Sp2, and Sp3 protein factors. By chromatin immunoprecipitation, Sp1 binds the cTnT promoter “in vivo.” Cotransfected Sp1 trans-activates the cTnT promoter in cardiomyocytes in culture. Sp3 represses Sp1-mediated transcriptional activation of the cTnT gene in embryonic cardiomyocytes. Sp3 repression of Sp1-mediated cTnT promoter activation is dose dependent, inferring a mechanism of competitive binding/inhibition. To evaluate the role of Sp factors in cardiac gene expression in vivo, we have established a clinically relevant animal model of pathological cardiac hypertrophy where the fetal cardiac program is activated. In this animal model, cardiac hypertrophy results from increased left-right shunting, volume loading of the left ventricle, and pressure loading of the right ventricle. Sp1 expression is increased in all four hypertrophied cardiac chambers, whereas Sp3 expression is diminished. This observation is consistent with the in vitro activating function of Sp1 and inhibitory effects of Sp3 on activity of cTnT promoter constructs. Sp factor levels are modulated during the hypertrophic cardiac program in vivo.

Enhancement of glycolysis in cardiomyocytes elevates endothelin-1 expression through the transcriptional factor hypoxia-inducible factor-1 α

2002 ◽  
Vol 103 (s2002) ◽  
pp. 210S-214S ◽  
Author(s):  
Yoshihiko KAKINUMA ◽  
Takashi MIYAUCHI ◽  
Takahiko SUZUKI ◽  
Koichi YUKI ◽  
Nobuyuki MURAKOSHI ◽  
...  
Keyword(s):  
Gene Expression ◽  
Electrical Stimulation ◽  
Energy Metabolism ◽  
Hypoxia Inducible Factor ◽  
Endothelin 1 ◽  
Cardiac Gene Expression ◽  
Cardiac Gene ◽  
Cultured Cardiomyocytes

We investigated whether the type of energy metabolism directly affects cardiac gene expression. During development, the heart switches from glycolysis to fatty acid β-oxidation in vivo, as demonstrated by the developmental switching of the major isoform of myosin heavy chain (MHC) from β to α. However, the β-MHC isoform predominates in monocrotaline-induced pulmonary hypertension, a model of right ventricular hypertrophy in vivo. Cultured cardiomyocytes showed a predominance of β-MHC expression over that of α-MHC, the same pattern as in the hypertrophied heart, suggesting that the in vitro condition itself causes the energy metabolism of cardiomyocytes to be switched to glycolysis. Electrical stimulation of cultured cardiomyocytes decreased the expression of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and hypoxia-inducible factor-1α (HIF-1α), but not that of peroxisome-proliferator-activated receptor-γ co-activator, suggesting that electrical stimulation suppresses the glycolytic system. Furthermore, a higher oxygen content (50%) decreased drastically the expression of GAPDH, HIF-1α and endothelin-1 (ET-1), and increased [3H]palmitate uptake. These findings indicate that the intrinsic energy metabolic system in cultured cardiomyocytes in vitro is predominantly glycolysis, and that the gene expression of cardiac ET-1 parallels the state of the glycolytic system. An antisense oligonucleotide against HIF-1α greatly decreased the gene expression of ET-1 and GAPDH, suggesting that cardiac ET-1 gene expression is regulated by cardiac energy metabolism through HIF-1α. In conclusion, it is suggested that the pattern of gene expression of ET-1 reflects the level of the glycolytic system in cardiomyocytes, and that enhanced glycolysis regulates the cardiac gene expression of ET-1 via HIF-1α.

scholarly journals Effect of amiodarone and dronedarone administration in rats on thyroid hormone-dependent gene expression in different cardiac components

2007 ◽  
Vol 156 (6) ◽  
pp. 695-702 ◽  
Author(s):  
I Stoykov ◽  
H C van Beeren ◽  
A F M Moorman ◽  
V M Christoffels ◽  
W M Wiersinga ◽  
...  
Keyword(s):  
Gene Expression ◽  
Thyroid Hormone ◽  
Thyroid Hormone Receptor ◽  
Left Ventricular ◽  
Cardiac Gene Expression ◽  
Specific Effects ◽  
Cardiac Gene ◽  
The Right ◽  
Different Parts

Objective: In view of their different actions on thyroid hormone receptor (TR) isoforms we set out to investigate whether amiodarone (AM) and dronedarone (Dron) have different and/or component-specific effects on cardiac gene expression. Design: Rats were treated with AM or Dron and the expression of TRα 1, TRα 2, TRβ 1 and several tri-iodothyronine (T3)-regulated genes was studied in different parts of the heart, namely the right atrium (RA), left ventricular wall (LVW) and apex. Methods: Rats were treated for 14 days with 100 mg/kg body weight AM or Dron. The expression of TRα 1, TRα 2, TRβ 1 and T3-regulated genes was studied using real-time PCR and non-radioactive in situ hybridisation. Results: AM and Dron affected TR expression in the RA similarly by decreasing TRα 1 and β 1 expression by about 50%. In the LVW, AM and Dron decreased TRβ 1 and, interestingly, AM increased TRα 1. In the apex, AM also increased TRα 2. The changes seen in T3-dependent gene expression are reminiscent of foetal reprogramming. Conclusion: Taken together, our results indicate that AM and Dron have similar effects on the expression of TR isoforms in the RA, which could partly contribute to their ability to decrease heart rate. On the other hand, the more profound effect of AM appears on TR- and T3-dependent gene expression in the left ventricle suggests foetal reprogramming.

Abstract 176: β-Adrenergic Receptor--Mediated Regulation of Cardiac Gene Expression Is Gefitinib Sensitive

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Douglas G Tilley ◽  
Jennifer A Talarico ◽  
Laurel A Grisanti ◽  
Rhonda L Carter
Keyword(s):  
Gene Expression ◽  
Regulation Of Gene Expression ◽  
Growth Factor Receptor ◽  
Sequencing Analysis ◽  
Egfr Transactivation ◽  
Cardiac Gene Expression ◽  
Cardiac Gene ◽  
Rapid Modulation ◽  
Acute Changes

BetaAR-mediated transactivation of epidermal growth factor receptor (EGFR) has been shown to promote cardioprotection in a mouse model of heart failure, however the mechanism(s) responsible for this pro-survival response are not known. We hypothesized that this transactivation event could impact a number of processes in the heart, including survival, via regulation of gene expression. To test the capacity of BetaAR-mediated EGFR transactivation to regulate this process, acute changes in cardiac gene expression were assessed via RNA sequencing in the hearts of C57BL/6 mice given i.p. injections of the BetaAR agonist isoproterenol (ISO, 1mg/kg) in the presence or absence of the EGFR antagonist gefitinib (Gef, 5mg/kg) for 1 hour. The total RNA from 4 hearts per treatment group (Control, ISO, Gef, Gef/ISO) were combined and underwent DNA library generation and SOLiD sequencing analysis, which revealed a substantial number of genes and isoforms regulated by each of the treatments. Interestingly, Gef alone significantly altered the expression of 270 genes compared to control suggesting potential Gef-dependent alterations in the heart during clinical use. ISO alone and Gef/ISO significantly altered 401 and 723 distinct genes compared to control, respectively. Further statistical analysis was performed between the ISO and Gef/ISO groups to assess true Gef sensitivity of ISO-regulated genes in the heart, confirming 173 genes significantly altered between the groups. Classification of these genes revealed 4 categories: ISO-dependent gene upregulation (1) or downregulation (2) antagonized by Gef, and ISO-dependent gene upregulation (3) or downregulation (4) promoted in presence of Gef. Identified within these categories were several genes known to be involved in the regulation of cardiac hypertrophy, apoptosis, sarcomeric structure and Ca2+-handling, which were selected for validation via qPCR. In conclusion, BetaAR-mediated EGFR transactivation induces rapid modulation of cardiac gene expression in response to catecholamine stimulation in vivo, with potential functional impacts on a number of cellular processes, while simultaneously acting to antagonize gene expression changes mediated via distinct BetaAR-mediated signaling pathways.

scholarly journals Age-associated Changes in Cardiac Gene Expression after Preconditioning

2009 ◽  
Vol 111 (5) ◽  
pp. 1052-1064 ◽  
Author(s):  
Lixin Liu ◽  
Jiang Zhu ◽  
Peter S. A. Glass ◽  
Peter R. Brink ◽  
Ira J. Rampil ◽  
...  
Keyword(s):  
Gene Expression ◽  
Early Phase ◽  
Cell Cycle Control ◽  
Transcriptional Response ◽  
Male Rats ◽  
Gene Chips ◽  
Cardiac Gene Expression ◽  
Anesthetic Preconditioning ◽  
Cardiac Gene

Background Cardiac protection afforded by ischemic preconditioning (IPC) and anesthetic preconditioning (APC) are significantly reduced in the senescent myocardium. The authors hypothesized that age would differentially modulate gene expression induced by IPC and APC in vivo. Methods Affymetrix RAT EXON ST 1.0 gene chips (Affymetrix, Santa Clara, CA) were used to explore the transcriptional response to IPC and APC in Fisher 344 male rats (young, 3-5 months, and old, 20-24 months, respectively). Both cohorts, young and old, were divided into three groups: (1) sham control, (2) IPC, and (3) APC. After a total of 90 min, the heart was removed, and the total RNA and protein were extracted. Results Thirty-one transcripts were increased in the young animals subjected to IPC, particularly transcriptional regulators (Atf3, Egr-1, Btg2, Egr2), cytokines (interleukin 6, CSF1, Myd88), chemokines (Cxcl10, Ccl2, Ccl7), regulators of growth and inflammation (Reg3g, Hamp), remodeling and cell adhesion migration (Cyr61, Tfpi2, Timp1), regulators of apoptosis/cell death (Birc3, Arntl, Hamp, Phlda1), and cell cycle control/DNA repairs (Rrad, Gadd45b, Gadd45g). In contrast, only one transcript increased (Atf3) in the old animals subjected to IPC. No changes in gene expression were found in the young or the old animals subjected to APC. Conclusions Early-phase IPC and APC induced different genomic responses. The absence of detectable changes associated with early-phase APC suggests a posttranscriptional or posttranslational mechanism. The absence of a genomic response in the senescent myocardium (except for IPC-induced Atf3) could underlie the failure of IPC to provide any cardiac protective benefit to older animals.

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