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  • atrial
  • Deep phenotyping of human induced pluripotent stem cell-derived atrial and ventricular cardiomyocytes. (semanticscholar.org)
  • 1,2 GATA4 is highly expressed in both embryonic and adult cardiomyocytes where it is thought to function as a key transcriptional regulator of numerous cardiac genes including atrial natriuretic factor (ANF), b-type natriuretic peptide (BNP), α-myosin heavy chain (α-MHC), β-MHC, and many others. (ahajournals.org)
  • Epidemiological data from the Framingham Heart Study and the Baltimore Longitudinal Study on Aging showed that in healthy populations there is an age-dependent increase in the prevalence of echocardiographic left ventricular (LV) hypertrophy, a decline in diastolic function, relatively preserved systolic function (ejection fraction) at rest, but a decline in exercise capacity (maximal ejection fraction) and an increased prevalence of atrial fibrillation. (ahajournals.org)
  • GATA4 is a zinc-finger transcription factor highly expressed in cardiomyocytes at different developmental stages where it regulates the transcription of several structural and regulatory genes, including atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), α- and β-myosin heavy chain (MHC). (ahajournals.org)
  • Repression of either gene results in the differentiating cardiomyocytes to move towards atrial chamber identity. (wikipedia.org)
  • However, molecular markers of hypertrophy (such as α-skeletal actin and atrial myosin light chain-1) were expressed with a wider distribution, suggesting that their induction was secondary to the expression of the transgene. (ahajournals.org)
  • fetal
  • As seen from the abnormalities from deletion of GATA4, it is essential for cardiac formation and the survival of the embryo during fetal development. (wikipedia.org)
  • GATA4 is not only important for cardiac development, but also development and function of the mammalian fetal ovary and contributes to fetal male gonadal development and mutations may lead to defects in reproductive development. (wikipedia.org)
  • These important results indicate that progression of the normal cardiomyocyte toward a failure phenotype is much more complex than simple reversal of fetal gene reprogramming, and that other genes directly involved in cell survival might also be reprogrammed and activated to preserve cellular homeostasis. (ahajournals.org)
  • Passive stretch in fetal cardiomyocytes induced differential CARP distribution at nuclei and I-band titin N2A regions. (wikipedia.org)
  • mutations
  • Mutations or defects in the GATA4 gene can lead to a variety of cardiac problems including congenital heart disease, abnormal ventral folding, and defects in the cardiac septum separating the atria and ventricles, and hypoplasia of the ventricular myocardium. (wikipedia.org)
  • This data could have important implications for human medicine by suggesting that mutations with the GATA4 transcription factor could be responsible for AV cushion defects in humans with improper septal formation leading to congenital heart disease. (wikipedia.org)
  • 3 In human hearts, GATA4 has also been demonstrated to be a critical regulator of cardiac development, as shown by the association between GATA4 mutations and the presence of congenital cardiac malformations. (ahajournals.org)
  • deletion
  • Traditional deletion of Gata4 caused embryonic lethality associated with endoderm defects and cardiac malformations, precluding an analysis of the role of GATA4 in the adult myocardium. (ahajournals.org)
  • However, cardiac-specific deletion of Gata4 resulted in a progressive and dosage-dependent deterioration in cardiac function and dilation in adulthood. (ahajournals.org)
  • 4 The specific effects of GATA4 deletion during embryonic age have been extensively investigated in genetically modified mouse models. (ahajournals.org)
  • Through a comprehensive microarray analysis the authors were able to show that GATA4 deletion significantly altered the expression patterns for a large number of genes of which at least three (PKCε, Bcl6, and caspase 12) are known to be involved in cell survival. (ahajournals.org)
  • embryonic
  • More recently, using a tetraploid embryo complementation strategy it has been possible to generate clonal embryonic day 9.5 Gata4 −/− embryos directly from embryonic stem cells and show that GATA4 is required for cardiogenesis. (ahajournals.org)
  • Afterwards, different membrane markers (Sca-1, Abcg-2, Flk-1) and transcription factors (Isl-1, Nkx2.5, GATA4) have been employed to identify and characterize these cells in the embryonic and adult life. (wikipedia.org)
  • interstitial
  • RESULTS: The latter resulted in significant LVH caused by both an increase in cardiomyocyte volume and interstitial collagen deposition. (uzh.ch)
  • cellular
  • In cellular senescence, ATM and ATR inhibit p62, an autophagy adaptor responsible for selective autophagy of GATA4. (wikipedia.org)
  • Necrotic cardiomyocytes with cellular infiltration, stromal edema with myocardial fibers dissociation, and the presence of polymorphonuclear cells can also be observed [ 6 - 8 ]. (hindawi.com)
  • During ventricular chamber formation, NKX2-5 and NKX2-7 are required to maintain cardiomyocyte cellular identity. (wikipedia.org)
  • p38α MAPK is implicated in diverse cellular function, from gene expression to programmed cell death through a network of signaling molecules and transcription factors. (wikipedia.org)
  • NKX2.5
  • In a clever strategy that used a GATA4-loxP-targeted allele together with 3 different cardiac-specific overexpressing Cre transgenes (α-MHC-Cre, β-MHC-Cre, and Nkx2.5-Cre), the authors dissected the role of GATA4 in cardiac remodeling of the normal heart and in response to both pathological and physiological stressors. (ahajournals.org)
  • NKX2.5 has been shown to interact with GATA4 and TBX5. (wikipedia.org)
  • NKX2.5 is dependent upon the JAK-STAT pathway and works along with MEF2, HAND1, and HAND2 transcription factors to direct heart looping during early heart development. (wikipedia.org)
  • NKX2.5 influences HAND1 and HAND2 transcription factors that control the essential asymmetrical development of the heart's ventricles. (wikipedia.org)
  • mRNA
  • 7 Moreover, expression of a dominant negative GATA4 or antisense GATA4 mRNA blocked features of cardiomyocyte hypertrophy induced by phenylephrine and endothelin-1 in culture. (ahajournals.org)
  • CARP was originally identified as a YB-1-associating, cardiac-restricted transcription co-repressor in the homeobox NKX2-5 pathway that is involved in cardiac ventricular chamber specification, maturation and morphogenesis, and whose mRNA levels are exquisitely sensitive to Doxorubicin, mediated through a hydrogen peroxide/ERK/p38MAP kinase-dependent as well as M-CAT cis-element-dependent mechanism. (wikipedia.org)
  • In cardiomyocytes treated with doxorubicin, a model of anthracycline-induced cardiomyopathy, CARP mRNA and protein levels were depleted, myofilament gene transcription was attenuated and sarcomeres showed significant disarray. (wikipedia.org)
  • protein
  • Transcription factor GATA-4 is a protein that in humans is encoded by the GATA4 gene. (wikipedia.org)
  • 1 Development of cardiac hypertrophy and HF is a complex process involving many aspects of alterations, such as abnormality of intracellular Ca 2+ homeostasis, activation of a variety of protein kinases, reprogramming of specific gene expression, disorders of metabolism, and so forth. (ahajournals.org)
  • p38α MAPK was originally identified as a tyrosine phosphorylated protein detected in activated immune cell macrophages with an essential role in inflammatory cytokine induction, such as Tumor Necrotic Factor α (TNFα). (wikipedia.org)
  • pathological
  • 11 Re-expression of the GATA4-regulated genes ANP, BNP, and β-MHC is considered a hallmark of pathological hypertrophy and heart failure, 11-13 and has been shown to correlate with the efficacy of drug therapy in dilative cardiomyopathy. (ahajournals.org)
  • serine
  • 10 Because both ERK1/2 and p38 MAPK receive input from diverse upstream signaling pathways, it suggested that serine 105 in GATA4 is a key convergence point in regulating the cardiac hypertrophic response. (ahajournals.org)
  • genes
  • Examination of gene expression profiles in the heart revealed a number of profound alterations in known GATA4-regulated structural genes as well as genes with apoptotic implications. (ahajournals.org)
  • Nuclear Factor Erythroid-derived 2-like 2 (Nrf2) senses oxidative environments and/or stress and initiates a cytoprotective response through transcriptional activation of antioxidant and detoxification genes. (biomedcentral.com)
  • Thus, acetylation of histones is known to increase the expression of genes through transcription activation. (wikipedia.org)
  • pathway
  • CONCLUSION: We show that sorafenib exhibits a regulatory role on the occurrence of LVH following AB in rats by blocking the rise in growth factors PDGF-BB and TGFβ1, activation of the corresponding c-Raf-ERK1/2 signaling pathway and effector mechanisms, including GATA4 and ANP. (uzh.ch)
  • cardiovascular
  • It interacts with a related transcription factor, GATA4, and is expressed primarily in the cardiovascular system and gonads. (invitae.com)
  • Age is a major risk factor for cardiovascular disease, at least in part because it prolongs exposure to hypertension, diabetes mellitus, hypercholesterolemia, and other cardiovascular risks. (ahajournals.org)
  • An Emerging Role for Krüppel-like Factors in Vascular Biology Trends in Cardiovascular Medicine. (jove.com)
  • pathways
  • Although a direct cause-and-effect relationship between NFAT-luciferase activity and pathological hypertrophy was not proven here, our results support the hypothesis that separable signaling pathways regulate pathological versus physiological hypertrophic growth of the myocardium, with calcineurin-NFAT potentially serving a regulatory role that is more specialized for maladaptive hypertrophy and heart failure. (ahajournals.org)
  • Cdk9 interacts adversely with Gq-dependent pathways for hypertrophy, impairing the expression of numerous genes for mitochondrial proteins, and, in particular, suppressing master regulators of mitochondrial biogenesis and function, perioxisome proliferator-activated receptor-γ coactivator-1 (PGC-1), and nuclear respiratory factor-1 (NRF-1). (ahajournals.org)
  • We seek to understand the role of mechanics in biology and force sensitive pathways in cell-cell adhesion and subcellular organization, the role of mechanical environment on the structure and function of stem cell derived cardiomyocytes as biophysical models of health and disease, and to develop models of mechanical signaling underlying the sense of touch and hearing. (stanford.edu)
  • Transcription factor pathways and congenital heart disease. (wikipedia.org)
  • induction
  • A review of studies examining cardiomyocyte cell cycle analysis and de novo cardiomyogenic induction in the adult heart is then presented. (ahajournals.org)
  • 5 Recent studies have elegantly identified several growth factors that regulate cardiomyogenic induction of the precursor cells in the anterior mesoderm. (ahajournals.org)
  • 6-9 ⇓ ⇓ ⇓ The failure of these growth factors to promote cardiomyogenic induction in more primitive precursor cells indicates that additional as of yet unidentified factors participate in the process. (ahajournals.org)
  • 1,2 Evolving knowledge of this phenotype, in reductionist molecular terms, has encompassed identifying genes whose induction or suppression is characteristic of hypertrophy, mapping the promoter regions of those genes to find the responsible transcription factor binding sites, and proving which transcription factors there bind DNA directly. (ahajournals.org)
  • Progesterone receptor-mediated induction of Krüppel-like factor 15 (KLF15), which can bind to GC-rich DNA within the E2F1 promoter, is required for maximal induction of E2F1 expression by progestins. (wikipedia.org)
  • kinase
  • The substrates of this kinase include transcription regulator ATF2, MEF2C, and MAX, cell cycle regulator CDC25B, and tumor suppressor p53, which suggest the roles of this kinase in stress-related transcription and cell cycle regulation, as well as in genotoxic stress response. (wikipedia.org)
  • repression
  • Gene activation or repression by DNA-binding factors also can depend on specific partners (coactivators or corepressors, including chromatin remodeling proteins) that are tethered to DNA indirectly, and the trafficking between the nuclear and cytoplasmic compartments of the cell likewise determines transcription factor activity. (ahajournals.org)
  • Repression of either gene results in the differentiating cardiomyocytes to move towards atrial chamber identity. (wikipedia.org)
  • promoter
  • Phosphorylation of RNAPII in the carboxyl terminal domain (CTD) of its largest subunit controls a number of critical steps subsequent to transcription initiation, among them enabling RNAPII to overcome its stalling in the promoter-proximal region and to engage in efficient transcription elongation. (ahajournals.org)
  • Using deletion and mutation analysis, EMSA and ChIP, demonstrated that USF1 and Spl can bind to E-box in-80 to-45 and GC-box in-189 to-155 in the KLF15 promoter respectively, thus regulating the transcription of KLF15 gene. (wikipedia.org)
  • stem cell
  • Briefly, eCSCs have been first identified through the expression of c-kit, the receptor of the stem cell factor and the absence of common hematopoietic markers, like CD45. (wikipedia.org)
  • cell
  • Calcineurin (PP2B) is a calcium/calmodulin-activated, serine-threonine phosphatase that transmits signals to the nucleus through the dephosphorylation and translocation of nuclear factor of activated T cell (NFAT) transcription factors. (ahajournals.org)
  • It is hoped that this compilation will serve to stimulate thought and experimentation in this intriguing area of cardiomyocyte cell biology. (ahajournals.org)
  • p38α MAPK is implicated in diverse cellular function, from gene expression to programmed cell death through a network of signaling molecules and transcription factors. (wikipedia.org)
  • nuclear
  • Calcineurin is activated by sustained elevations in intracellular calcium, which facilitates binding to its primary downstream effector, nuclear factor of activated T cells (NFAT). (ahajournals.org)
  • p300 acts as a calcineurin-regulated nuclear factors of activated T lymphocytes (NFATc), downstream targets of calcineurin. (ahajournals.org)
  • 7 Calcium-activated phosphatase, calcineurin, dephosphorylates the serine residues of the calcineurin-regulated nuclear factors of activated T lymphocytes (NFATc) and unmasks its nuclear localization sequences. (ahajournals.org)
  • contrast
  • In contrast, physiological hypertrophy as produced in two separate models of exercise training failed to show significant calcineurin-NFAT coupling in the heart at multiple time points, despite measurable increases in heart to body weight ratios. (ahajournals.org)