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At least 451 records · Page 25Linked to original sources
PubMed1987

Calcium antagonists and the developing heart.

Ontogenetic differences in cardiac sensitivity to calcium antagonists were studied in chick embryonic and postnatal immature rat heart. It has been found that verapamil exhibits no protective effect on isoprenaline-induced changes of the chick embryonic heart. Furthermore, it increased the mortality of experimental embryos. The mortality of verapamil-treated rats was age-dependent, increasing with decreasing age of animals. Similarly, the intensity of negative inotropic response of the isolated right ventricular myocardium and isolated perfused rat heart was significantly greater in the youngest age groups. These results point to the possible negative consequences of the clinical use of calcium antagonists during the early phases of ontogeny.

Age Factors↗
PubMed1982

Biophysics of the developing heart. III. A comparison of the left ventricular dynamics of the fetal and neonatal lamb heart.

Changes in heart rate, left ventricular dimensions, and inotropic state of chronically instrumented lambs from in utero to neonatal life are described and analyzed. Six lambs were instrumented from 5 to 23 days prior to parturition and studied prior to and after birth. Heart rate, aortic systolic and diastolic pressure, left ventricular end-diastolic and peak systolic pressure, and left ventricular minor axis end-diastolic (EDD) and end-systolic dimension (ESD) were monitored. The maximum rate of rise of left ventricular pressure (Pmax), percentage fractional shortening [(EDD - ESD divided by EDD) x 100%; %FS], and the Pmax -interval ratio (this ratio of Pmax of the postextrasystolic potentiated systole to Pmax of the previous regular systole is independent of volume) described contractility. Subsequent to birth: heart rate, aortic systolic and diastolic pressure and left ventricular dimensions increased; during spontaneous rhythm and at equal fetal and neonatal heart rates and ventricular dimensions, %FS and P max increased significantly; and P max -interval ratio changed significantly. An increase in myocardial inotropic state occurs with birth. This enhancement is in addition to the effects of the increase in heart rate and end-diastolic volume that occur with the adaptation to birth.

Adaptation, Physiological↗
PubMed1994

GATA-4/5/6, a subfamily of three transcription factors transcribed in developing heart and gut.

We describe experiments which show that: 1) two previously identified members of the GATA family of transcription factors (both of which were originally called GATA-4) correspond to chicken cDNAs for two distinct factors (which we now refer to as cGATA-4 and cGATA-5); 2) another new member of this family corresponds to a third factor designated cGATA-6; 3) each of these mRNAs displays a differential expression pattern. The cGATA-5 gene is initially transcribed in the cardiac crescent prior to formation of the primordial heart tube. Following formation of the primitive heart, cGATA-5 transcripts are evident in both endocardium and myocardium as well as in other lateral plate derivatives. The cGATA-5 gene is also transcribed in the primitive embryonic gut and in late stage embryos is sequentially up-regulated in distinct segments of gastrointestinal epithelia as they undergo terminal differentiation. These studies thus provide novel insights into tissue-specific regulation by GATA-5, as well as into possibly overlapping regulatory functions for these three family members.

Animals↗
PubMed1998

Mechanical aspects of cardiac development.

Heart development depends on a dynamic interaction between genetic and epigenetic factors. This paper discusses some of the biomechanical processes that help shape the heart in the embryo. First, an overview is given of some of the critical events that occur during cardiac development. Next, mechanics and modeling strategies are discussed for the morphogenetic processes of cardiac tube formation, cardiac looping, myocardial trabeculation, septation, valve formation, and muscle-fiber alignment. Finally, some considerations for future work in this area are listed.

Animals↗
PubMed1994

Identification of novel protein kinases expressed in the myocardium of the developing mouse heart.

In Drosophila and Caenorhabditis, signal transduction pathways initiated by the activation of receptor-protein tyrosine kinases can mediate developmental fate decisions. In order to examine whether similar mechanisms are employed during mammalian embryogenesis, we undertook a search for novel protein kinases expressed during heart development in the mouse. The primitive mouse heart is formed between 7.75 and 8.5 days post coitum (dpc) and consists of myocardial and endocardial cells. A reverse transcriptase polymerase chain reaction-based approach was used to amplify protein kinase specific products from cDNAs obtained from 8.5 dpc heart tissue. Twenty independent PCR products corresponding to either protein serine/threonine or tyrosine kinases were identified. In this report, we describe the characterization of two of the genes corresponding to the novel PCR products (designated Hek2 and msk). Hek2 encodes the mouse ortholog of human HEK2, a recently identified member of the eph receptor-protein tyrosine kinase gene family. Prior to and at the time of heart formation (7.5-8.0 dpc), Hek2 is expressed in the cranial (rostral) region of the embryo from which a subpopulation of cells will give rise to the rudimentary heart. Between 8.0 and 9.5 dpc, Hek2 mRNA expression is observed in myocardial cells, head mesenchyme and paraxial mesoderm. Hek2 transcripts are not detected in endocardial cells. After 9.5 dpc, Hek2 expression is downregulated. msk (for myocardial SNF1-like kinase) encodes a putative protein serine/threonine kinase most similar to the yeast gene SNF1. msk mRNA expression is restricted to myocardial cells and their progenitors in the 7.75-8.5 dpc developing heart. Subsequently, msk mRNA expression is rapidly downregulated. The patterns of Hek2 and msk expression suggest that these protein kinases may function during development of the primitive heart.

Amino Acid Sequence↗
PubMed2002

Regulation of apoptosis in the endocardial cushions of the developing chick heart.

During the early stages of heart development, there are two main foci of cell death: outflow tract (OT) and atrioventricular (AV) endocardial cushions. These tissues contribute to the septa and valves of the mature heart and receive cell populations from neural crest (NC) cell migration and epicardial cell invasion. We examined embryonic chick hearts for expression, in the cushions, of bcl-2 family members, caspase-9, and the caspase substrate poly(ADP-ribose) polymerase. Antiapoptotic bcl-2 is expressed heavily in the OT and AV regions throughout embryonic days (ED) 4-7, with a decrease in levels at ED 4 and 5 in OT and AV cushions, respectively. Proapoptotic bax predominantly associated with the prongs of the NC-derived aorticopulmonary (AP) septum but was expressed throughout the AV cushions. Proapoptotic bak also associated with the prongs of the AP septum in the OT, while protein levels were upregulated at ED 4-5 and 4-6 in OT and AV cushions, respectively. Bid expression showed a similar time course. We found the 10-kDa cleavage fragment of active caspase-9 at ED 4-8 and 5-8 in OT and AV cushions, respectively, and the 24-kDa cleavage fragment of poly(ADP-ribose) polymerase throughout ED 3-8 and 7-8 in OT and AV cushions, respectively. Caspase-3 cleavage occurred throughout the time period examined. Using cushion cell cultures, we found that inhibitors of caspases-3 and -9 and a universal caspase inhibitor significantly reduced apoptosis, as did retroviral overexpression of bcl-2 using an RCAS expression vector. Premigratory NC cells were fluorescently labeled in vivo with 1,1-didodecyl-3,3,3',3'-tetramethylindocarbocyanine. Subsequent nuclear staining of cushion cells with 4,6-diamidino-2-phenylindole revealed the presence of apoptotic nuclei in the NC cells in the OT cushions and in the prongs of the AP septum. These results demonstrate a developmentally regulated role for the bcl-2 and the caspase families of molecules in the endocardial cushions of the developing heart and lend support to the possibility that some of the dying cells in the cushions are derived from the NC.

Animals↗
PubMed1996

The heart and development.

The perspective from which the developing heart is viewed can lead to differing conclusions about the effects of development on cardiac function. The hearts of the embryo, fetus and adult, viewed from a global perspective, sustain the circulation through the same basic mechanisms of developing pressure and ejecting blood. The failure of the embryonic heart to perform these tasks results in growth failure, edema, and embryonic death, just as in the infant and adult such failure results in premature death. Furthermore, from the viewpoint of gross anatomy, following embryonic morphogenesis, the developing and adult hearts appear in general to be structurally similar, differing only in size and mass. However, a closer view shows, in the molecular and structural makeup of the myocardium, richly complex changes that can modulate the basic physiological properties of the cardiac myocyte. This article focuses on how these changes and the effects of birth and development alter ventricular function.

Adult↗
PubMed1996

Regulation of DNA synthesis of myocardial and epicardial cells in developing rat heart by [Met5]enkephalin.

Endogenous opioids serve as negative growth factors in neural and nonneural tissues in addition to being neuromodulators. This study investigated the hypothesis that native opioid peptides are inhibitory growth factors in heart development. DNA synthesis of ventricular myocardial and epicardial cells in 1-day-old rats was examined. Administration of a variety of opioids and peptides revealed that [Met5]enkephalin had the greatest inhibitory effect on DNA synthesis; peptides related to mu-, delta-, kappa-, epsilon-, and sigma-receptors had no influence on cell proliferation, even at concentrations as high as 10 mg/kg. [Met5]enkephalin, also termed opioid growth factor (OGF), depressed DNA synthesis at 1 and 10 mg/kg but not at 0.01 or 0.1 mg/kg. The effects of OGF were noted within 1 h of treatment, persisted for as long as 22 h after drug administration, and could depress DNA synthesis in myocardial and epicardial cells to 43 and 36%, respectively, of control values. The effect of OGF on DNA synthesis of heart cells was opioid receptor-mediated. Organ culture experiments revealed that opioids acted directly on developing cardiac cells. Both OGF and its receptor, zeta, were detected in heart cells of 1-day-old rats by immunocytochemistry. mRNA for preproenkephalin, the precursor to OGF, was observed in 1-day-old rat heart. These results indicate that an autocrine- or paracrine-produced endogenous opioid peptide (i.e., OGF) and its receptor (i.e., zeta) are present in the developing heart and govern DNA synthesis, with OGF acting directly as a tonic negative regulator of cell generation.

Aging↗
PubMed1995

Intermediate filaments in cardiac myogenesis: nestin in the developing mouse heart.

By using immunohistology combined with immunoblotting, cell culture, and RT-PCR, we show that the intermediate filament protein nestin is transiently expressed in the midembryonic mouse heart. Monoclonal antibody (MAb) Rat-401, known to react with nestin in neural and skeletal muscle cells, was also found to react with ventricular and atrial cells throughout the mouse heart from embryonic day 9 (E9) through E10.5. Both before (E8.5) and after (E11-adult) this brief period, staining with Rat-401 was absent from atrial and ventricular myocytes. To evaluate the specificity of staining with MAb Rat-401 in the heart, we used immunoblotting, cell culture, and RT-PCR to verify that the authentic nestin protein and mRNA were expressed in cardiomyocytes of the E10 mouse. Nestin expression is the first molecular marker for this distinct midembryonic period of heart development.

Animals↗
PubMed2000

Sequential programs of retinoic acid synthesis in the myocardial and epicardial layers of the developing avian heart.

Endogenous patterns of retinoic acid (RA) signaling in avian cardiac morphogenesis were characterized by localized expression of a key RA-synthetic enzyme, RALDH2, which displayed a biphasic pattern during heart development. RALDH2 immunoreactivity was initially apparent posterior to Hensen's node of stage 5-6 embryos and subsequently in somites and unsegmented paraxial and lateral plate mesoderm overlapping atrial precursors in the cardiogenic plate of stage 9- embryos. Initial RALDH2 synthesis in the posterior myocardium coincided with activation of the AMHC1 gene, a RA-responsive marker of inflow heart segments. A wave of RALDH2 synthesis then swept the myocardium in a posterior-to-anterior direction, reaching the outflow tract by stage 13, then fading from the myocardial layer. The second phase of RALDH2 expression, initiated at stage 18 in the proepicardial organ, persisted in migratory epicardial cells that completely enveloped the heart by stage 24. Early restriction of RALDH2 expression to the posterior cardiogenic plate, overlapping RA-inducible gene activation, provides evidence for commitment of posterior avian heart segments by localized production of RA, whereas subsequent RALDH2 expression exclusively in the migratory epicardium suggests a role for the morphogen in ventricular expansion and morphogenesis of underlying myocardial tissues.

Aldehyde Oxidoreductases↗
PubMed2001

CHAMP, a novel cardiac-specific helicase regulated by MEF2C.

MEF2C is a MADS-box transcription factor required for cardiac myogenesis and morphogenesis. In MEF2C mutant mouse embryos, heart development arrests at the looping stage (embryonic day 9.0), the future right ventricular chamber fails to form, and cardiomyocyte differentiation is disrupted. To identify genes regulated by MEF2C in the developing heart, we performed differential array analysis coupled with subtractive cloning using RNA from heart tubes of wild-type and MEF2C-null embryos. Here, we describe a novel MEF2C-dependent gene that encodes a cardiac-restricted protein, called CHAMP (cardiac helicase activated by MEF2 protein), that contains seven conserved motifs characteristic of helicases involved in RNA processing, DNA replication, and transcription. During mouse embryogenesis, CHAMP expression commences in the linear heart tube at embryonic day 8.0, shortly after initiation of MEF2C expression in the cardiogenic region. Thereafter, CHAMP is expressed specifically in embryonic and postnatal cardiomyocytes. At the trabeculation stage of heart development, CHAMP expression is highest in the trabecular region in which cardiomyocytes have exited the cell cycle and is lowest in the proliferative compact zone. These findings suggest that CHAMP acts downstream of MEF2C in a cardiac-specific regulatory pathway for RNA processing and/or transcriptional control.

Amino Acid Sequence↗
PubMed2000

Ventricular expression of tbx5 inhibits normal heart chamber development.

The T-box gene tbx5 is expressed in the developing heart, forelimb, eye, and liver in vertebrate embryos during critical stages of morphogenesis and patterning. In humans, mutations in the TBX5 gene have been associated with Holt-Oram syndrome, which is characterized by developmental anomalies in the heart and forelimbs. In chicken and mouse embryos, tbx5 expression is initiated at the earliest stages of heart formation throughout the heart primordia and is colocalized with other cardiac transcription factors such as nkx-2.5 and GATA4. As the heart differentiates, tbx5 expression is restricted to the posterior sinoatrial segments of the heart, consistent with the timing of atrial chamber determination. The correlation between tbx5 expression and atrial lineage determination was examined in retinoic acid (RA)-treated chicken embryos. tbx5 expression is maintained throughout the hearts of RA-treated embryos under conditions that also expand atrial-specific gene expression. The downstream effects of persistent tbx5 expression in the ventricles were examined directly in transgenic mice. Embryos that express tbx5 driven by a beta-myosin heavy chain promoter throughout the primitive heart tube were generated. Loss of ventricular-specific gene expression and retardation of ventricular chamber morphogenesis were observed in these embryos. These studies provide direct evidence for an essential role for tbx5 in early heart morphogenesis and chamber-specific gene expression.

Animals↗