• 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)
  • Cardiac aging in mice is accompanied by accumulation of mitochondrial protein oxidation, increased mitochondrial DNA mutations and deletions and mitochondrial biogenesis, increased ventricular fibrosis, enlarged myocardial fiber size, decreased cardiac SERCA2 protein, and activation of the calcineurin-nuclear factor of activated T-cell pathway. (ahajournals.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)
  • GATA4 mutations can predispose to dilated cardiomyopathy (CMD), a disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. (abcam.com)
  • myocardium
  • Flt1+/Flt4+ CPCs derived from iPSCs were shown to engraft into the adult myocardium and robustly differentiate into cardiomyocytes with phenotypic and electrophysiologic characteristics of adult cardiomyocytes. (wikipedia.org)
  • With the myocardium now recognized as a tissue with limited regenerating potential, harbouring eCSCs that can be isolated and amplified in vitro for regenerative protocols of cell transplantation or stimulated to replicate and differentiate in situ in response to growth factors, it has become reasonable to exploit this endogenous regenerative potential to replace lost/damaged cardiac muscle with autologous functional myocardium. (wikipedia.org)
  • mice
  • This protocol yields a consistent result for the culture of functional adult cardiomyocytes from a variety of genetically modified mice. (jove.com)
  • GATA4 inactivation, with GATA4-null mice, leads to down regulation of Erbb3 and altered Erk expression, two other important molecules in EMT and ventricular inlet separation. (wikipedia.org)
  • 5-7 Mice homozygous for a GATA4 null allele 6 or homozygous GATA4-deficient mice (GATA4 −/− ) 5 die early in development because of abnormal embryogenesis and heart tube formation. (ahajournals.org)
  • At baseline, there was no difference in morphology of cardiomyocyte and heart and cardiac contractility between RyR-2 +/− and wild-type mice, although Ca 2+ release from sarcoplasmic reticulum was impaired in isolated RyR-2 +/− cardiomyocytes. (ahajournals.org)
  • deletion
  • However, cardiac-specific deletion of Gata4 resulted in a progressive and dosage-dependent deterioration in cardiac function and dilation in adulthood. (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)
  • fibrosis
  • Elevated NADPH oxidase 4 (NOX4)-derived hydrogen peroxide (H 2 O 2 ) supported by concomitant decreases in nitric oxide (NO) signaling and reactive oxygen species scavengers are central factors in the molecular pathogenesis of fibrosis in numerous tissues and organs. (hindawi.com)
  • protein
  • 4,6,9-13 We have previously observed that agonist stimulation results in phosphorylation of GATA4 at serine 105 through the direct action of extracellular signal-regulated kinase (ERK) 1/2 and p38 mitogen-activated protein kinase (MAPK). (ahajournals.org)
  • 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)
  • 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)
  • ET-1 induces cardiac gene transcription and protein expression of antiapoptotic B cell leukemia-2 (bcl-2) in a calcineurin-dependent manner. (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)
  • Krüppel-like factor 15 is a protein that in humans is encoded by the KLF15 gene in the Krüppel-like factor family. (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 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)
  • autophagy
  • GATA4 is regulated through the autophagy-lysosome pathway in eukaryotic cells. (wikipedia.org)
  • In cellular senescence, ATM and ATR inhibit p62, an autophagy adaptor responsible for selective autophagy of GATA4. (wikipedia.org)
  • adult heart
  • These data nicely demonstrate the important role GATA4 plays as a regulator of gene expression to maintain normal cardiac homeostatic remodeling in the unstressed adult heart by promoting cell survival and inhibiting programmed cell death. (ahajournals.org)
  • dysfunction
  • 16 , 17 Numerous lines of clinical and experimental evidence have indicated that altered RyR-2 gene and function contribute to cardiac disorders, including catecholaminergic polymorphic ventricular tachycardia or arrhythmogenic right ventricular cardiomyopathy type 2, 15 cardiac hypertrophy, and dysfunction. (ahajournals.org)
  • 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)
  • endothelial
  • Transcriptional profiling studies identified the Kruppel-like factor (KLF)2 as being inhibited by the inflammatory cytokine interleukin-1beta and induced by laminar shear stress in cultured human umbilical vein endothelial cells. (jove.com)
  • induction
  • 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)
  • 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)
  • heart
  • 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)
  • 1 LV hypertrophy is well known to increase the risk of coronary heart disease, stroke, and sudden death. (ahajournals.org)
  • Prolonged hypertrophy, however, may eventually lead to heart failure (HF). (ahajournals.org)
  • NKX 2.5 is a transcription factor that regulates heart development from the Cardiac Crescent of the splanchnic mesoderm in humans. (wikipedia.org)
  • 9 10 Although a number of transcription factors have been isolated that are expressed in the heart, 11 12 none of these has been shown to be cardiac specific. (ahajournals.org)
  • Cardiac hypertrophy leading to heart failure remains a leading cause of morbidity and mortality in the 21st century despite major therapeutic advances. (ed.ac.uk)
  • During hypertrophy and heart failure, Nppa expression is reactivated in the ventricles and serves as a highly conserved marker of heart disease. (ahajournals.org)