Regulation of cardiac gene expression during myocardial growth and hypertrophy: molecular studies of an adaptive physiologic response

  title={Regulation of cardiac gene expression during myocardial growth and hypertrophy: molecular studies of an adaptive physiologic response},
  author={Kenneth R Chien and Kirk U. Knowlton and Gao Zhu and Shu Chien},
  journal={The FASEB Journal},
  pages={3037 - 3046}
Studies from both in vivo and in vitro model systems have provided an initial skeleton of the potential signaling pathways that might regulate cardiac genes during growth and hypertrophy. One of the first detectable changes in cardiac gene expression is the activation of a program of immediate early gene expression, which is distinct for the hypertrophic response, and is conserved in multiple models of both in vivo and in vitro hypertrophy. Diverse and distinct hormonal stimuli have been… 
Expression of nuclear-acting early-response genes in the rat heart : implications for cardiac hypertrophy
The in vivo results lend further support to the notion that the products of early-response genes structurally or functionally related to c-fos may mediate the hypertrophic actions of norepinephrine and pressure overload, which may be associated with the proliferation of cardiac non-myocyte cells which occurs concomitant with cardiac hypertrophy.
Signaling mechanisms for the activation of an embryonic gene program during the hypertrophy of cardiac ventricular muscle.
  • R. Chien
  • Biology
    Basic research in cardiology
  • 1992
Co-transfection of a dominant negative RAS vector effectively inhibits the induction of the ANF gene during alpha adrenergic mediated hypertrophy of ventricular muscle cells, thereby establishing that a RAS-mediated pathway is required for ANF induction.
The role of protein kinases in adaptational growth of the heart.
Cellular mechanisms of cardiac hypertrophy
A critical overview of the signalling pathways involved in the hypertrophic response is provided and a scheme to account for many of its features is provided.
Divergent transcriptional responses to independent genetic causes of cardiac hypertrophy.
Rather than identifying a single common hypertrophic cardiomyopathy gene program, data suggest that extensive groups of genes may be useful for the prediction of specific underlying genetic determinants and condition-specific therapeutic approaches.
Mitogen-activated protein kinases mediate changes in gene expression, but not cytoskeletal organization associated with cardiac muscle cell hypertrophy
It is found that phenylephrine treatment results in the activation of the MAP kinases and that this activity is required for transactivation of the fos, ANF, and MLH promoters, which suggests that the signal transduction pathways leading to different hypertrophic responses diverge upstream of theMAP kinases but possibly downstream of Ras.
The Role of the Transcription Factor Nuclear Factor Kappa B in the Regulation of Cardiac Hypertrophy
Recently described mechanisms of inhibition of NF-κB activity and their application to animal models of cardiac hypertrophy are focused on and could be helpful for future studies that will be focused on the research of specific and non-toxic inhibitors of NLKB activity to regulate cardiachypertrophy and its evolution towards heart failure.


Protooncogene induction and reprogramming of cardiac gene expression produced by pressure overload.
Results suggest that induction of cellular protooncogenes and heat shock (stress) protein genes is an early response to pressure overload, whereas reinduction of the genes normally expressed only in perinatal life, such as fetal isoforms of contractile proteins and atrial natriuretic factor, is a later event.
Peptide growth factors can provoke "fetal" contractile protein gene expression in rat cardiac myocytes.
Cardiac-specific gene expression is intricately regulated in response to developmental, hormonal, and hemodynamic stimuli. To test whether cardiac muscle might be a target for regulation by peptide
Phorbol esters induce immediate-early genes and activate cardiac gene transcription in neonatal rat myocardial cells.
A gene inducible by serum growth factors encodes a member of the steroid and thyroid hormone receptor superfamily.
Results suggest that the growth factor-inducible immediate early gene nur/77 encodes a ligand-binding protein that regulates the genomic response to growth factors.
Cardiac myocyte hypertrophy is associated with c-myc protooncogene expression.
The findings show that the induction of cardiac myocyte hypertrophy is associated with enhanced expression of the c-myc gene and suggest that hormonally induced cellhypertrophy and cell division share common mechanistic pathways.
Alpha 1-adrenergic receptor stimulation of sarcomeric actin isogene transcription in hypertrophy of cultured rat heart muscle cells.
The alpha 1-adrenoceptor mediates a rapid, transient, and selective increase in transcription of the sarcomeric actin isogenes during cardiac myocyte hypertrophy, demonstrating that transcriptional induction via the alpha 1 receptor is complex and may involve preexisting regulatory factors.
Stretching cardiac myocytes stimulates protooncogene expression.
Myosin heavy chain messenger RNA and protein isoform transitions during cardiac hypertrophy. Interaction between hemodynamic and thyroid hormone-induced signals.
The results suggest that the MHC isozyme transition during hemodynamic overload is mainly regulated by pretranslational mechanisms, and that a complex interplay exists between hemodynamic and hormonal stimuli in MHC gene expression.
Biochemical mechanisms of cardiac hypertrophy.
Overall, increased capacity for, and efficiency of, protein synthesis are the major factors accounting for cardiac growth.