Human Fetal Heart Research Articles

Immunohistochemical distribution of desmin in the human fetal heart.

Desmin is a member of the intermediate filaments, which play crucial roles in the maturation, maintenance and recovery of muscle fibers. Its expression has been examined in human cardiac muscle, rat and chicken, but its spatial distribution in the human fetal heart has not been described. The present study investigated desmin expression in the human fetal heart and associated great vessels in 14 mid-term fetuses from 9 to 18 weeks of gestation. Immunoreactivity for myosin heavy chain (MHC) and alpha smooth muscle actin (α-SMA), as well as neuron-specific enolase (NSE), was also examined. Increased expression of desmin from 9 to 18 weeks was clearly localized in the atrial wall, the proximal portions of the pulmonary vein and vena cava, and around the atrioventricular node. Desmin-positive structures were also positive for MHC. Meanwhile, the great vessels were also positive for α-SMA. The distribution of desmin exhibited a pattern quite different from that described in previous studies of rat and chicken. Thus, desmin in the human fetal heart does not seem to play a general role in myocardial differentiation but rather a specific role closely related to the maturation of the α-isozyme of MHC. Desmin expression in the developing fetal heart also appeared to be induced by mechanical stress due to the involvement of venous walls against the atrium.

Temporal and spatial performance of vector velocity imaging in the human fetal heart

To assess the spatial and temporal performance of fetal myocardial speckle tracking, using high-frame-rate (HFR) storing and Lagrangian strain analysis. Dummy electrocardiographic signaling permitted DICOM HFR in 124 normal fetuses and paired low-frame-rate (LFR) video storing at 25 Hz in 93 of them. Vector velocity imaging (VVI) tracking co-ordinates were used to compare time and spatial domain measures. We compared tracking success, Lagrangian strain, peak diastolic velocity and positive strain rate values in HFR vs. LFR video storing. Further comparisons within an HFR subset included Lagrangian vs. natural strain, VVI vs. M-mode annular displacement, and VVI vs. pulsed-wave tissue Doppler imaging (TDI) peak velocities. HFR (average 79.4 Hz) tracking was more successful than LFR (86 vs. 76%, P = 0.024). Lagrangian and natural HFR strain correlated highly (left ventricle (LV): r = 0.883, P < 0.001; right ventricle (RV): r = 0.792, P < 0.001) but natural strain gave 20% lower values, suggesting reduced reliability of measurement. Lagrangian HFR strain was similar in LV and RV and decreased with gestation (P = 0.015 and P < 0.001, respectively). LV Lagrangian LFR strain was significantly lower than the values for the RV (P < 0.001) and those using paired LV-HFR recordings (P = 0.007). Annular displacement methods correlated highly (LV = 1.046, r = 0.90, P < 0.001; RV = 1.170, r = 0.88, P < 0.001). Early diastolic waves were visible in 95% of TDI, but in only 26% of HFR and 0% of LFR recordings, and HFR-VVI velocities were significantly lower than those for TDI (P < 0.001). Doppler estimation of velocities remains superior to VVI but image gating and use of original co-ordinates should improve offline VVI assessment of fetal myocardial function.

Assessment of Left Ventricular Pre-Ejection Period in the Fetus Using Simultaneous Magnetocardiography and Echocardiography

Introduction: Fetal magnetocardiography (fMCG) is a promising new technique for assessing fetal rhythm; however, no prior studies have utilized fMCG to evaluate human fetal electromechanical physiology. Pre-ejection period (PEP) is an important measure of the electromechanical activation of the heart, and is altered by disease states and arrhythmias. Materials and Methods: A novel technique was used to assess fetal PEP and its relationship to other fetal systolic time intervals, RR interval, and gestational age (GA). 25 normal human fetuses between 19 and 38 weeks’ gestation were studied using simultaneous pulsed Doppler ultrasound and fMCG. Correlations among PEP, ejection time, QRS width and RR interval were assessed using linear regression. Results: Across all subjects, PEP was found to correlate with GA (R = 0.57, p < 0.0001), QRS width (R = 0.35, p = 0.026), and RR interval (R = 0.37, p = 0.018). In individual sessions, PEP negatively correlated beat-to-beat with the preceding RR interval. Conclusion: PEP exhibits developmental trends that provide a better understanding of the normal development of the human fetal heart.

Cardiomyocyte Clusters Derived from Human Embryonic Stem Cells Share Similarities with Human Heart Tissue

Cardiotoxicity testing is a key activity in the pharmaceutical industry in order to detect detrimental effects of new drugs. A reliable human in vitro model would both be beneficial in selection of lead compounds and be important for reducing animal experimentation. However, the human heart is a complex organ composed of many distinct types of cardiomyocytes, but cardiomyocyte clusters (CMCs) derived from human embryonic stem cells could be an option for a cellular model. Data on functional properties of CMCs demonstrate similarities to their in vivo analogues in human. However, development of an in vitro model requires a more thorough comparison of CMCs to human heart tissue. Therefore, we directly compared individually isolated CMCs to human fetal, neonatal, adult atrial and ventricular heart tissues. Real-time qPCR analysis of mRNA levels and protein staining of ion channels and cardiac markers showed in general a similar expression pattern in CMCs and human heart. Moreover, a significant decrease in beat frequency was noted after addition of Zatebradine, a blocker to I(f) involved in regulation of spontaneous contraction in CMCs. The results underscore the similarities of CMCs to human cardiac tissue, and further support establishment of novel cardiotoxicity assays based on the CMCs in drug discovery.

Mesomelia-Synostoses Syndrome Results from Deletion of SULF1 and SLCO5A1 Genes at 8q13

Mesomelia-synostoses syndrome (MSS) or mesomelic dysplasia with acral synostoses Verloes-David-Pfeiffer type is a rare autosomal-dominant disorder characterized by mesomelic limb shortening, acral synostoses, and multiple congenital malformations. So far, five patients in four unrelated families have been reported worldwide with MMS. By using whole-genome oligonucleotide array CGH, we have identified an interstitial deletion at 8q13 in all patients. The deletions vary from 582 Kb to 738 Kb in size, but invariably encompass only two genes: SULF1, encoding the heparan sulfate 6-O-endosulfatase 1, and SLCO5A1, encoding the solute carrier organic anion transporter family member 5A1. SULF1 acts as a regulator of numerous growth factors in skeletal embryonic development whereas the function of SLCO5A1 is yet unknown. Breakpoint sequence analyses performed in two families showed nonrecurrent deletions. Real-time quantitative RT-PCR analysis showed the highest levels of SULF1 transcripts in human osteoblasts and cartilage whereas SLCO5A1 was highly expressed in human fetal and adult brain and heart. Our results strongly suggest that haploinsufficiency of SULF1 contributes to this mesomelic chondrodysplasia, highlighting the critical role of endosulfatase in human skeletal development. Codeletion of SULF1 and SLCO5A1--which does not result from a low-copy repeats (LCRs)-mediated recombination event in at least two families--was found in all patients, so we suggest that haploinsufficiency of SULF1 combined with haploinsufficiency of SLCO5A1 (or the altered expression of a neighboring gene through position effect) could be necessary in the pathogenesis of MSS.

Arrhythmias Presenting in Neonatal Lupus

Perfusion of human foetal heart with anti-Ro/SSA antibodies induces transient heart block. Anti-Ro/SSA antibodies may cross-react with T- and L-type calcium channels, and anti-p200 antibodies may cause calcium to accumulate in rat heart cells. These actions may explain a direct electrophysiological effect of these antibodies. Congenital complete heart block is the more severe manifestation of so-called "Neonatal Lupus". In clinical practice, it is important to distinguish in utero complete versus incomplete atrioventricular (AV) block, as complete AV block to date is irreversible, while incomplete AV block has been shown to be potentially reversible after fluorinated steroid therapy. Another issue is the definition of congenital AV block, as cardiologists have considered congenital blocks detected months or years after birth. We propose as congenital blocks detected in utero or within the neonatal period (0-27 days after birth). The possible detection of first degree AV block in utero, with different techniques, might be a promising tool to assess the effects of these antibodies. Other arrhythmias have been described in NL or have been linked to anti-Ro/SSA antibodies: first degree AV block, in utero and after birth, second degree (i.e. incomplete block), sinus bradycardia and QT prolongation, both in infants and in adults, ventricular arrhythmias (in adults). Overall, these arrhythmias have not a clinical relevance, but are important for research purposes.

Fetal cardiac arrhythmia detection and in utero therapy

The human fetal heart develops arrhythmias and conduction disturbances in response to ischemia, inflammation, electrolyte disturbances, altered load states, structural defects, inherited genetic conditions, and many other causes. Yet sinus rhythm is present without altered rate or rhythm in some of the most serious electrophysiological diseases, which makes detection of diseases of the fetal conduction system challenging in the absence of magnetocardiographic or electrocardiographic recording techniques. Life-threatening changes in QRS or QT intervals can be completely unrecognized if heart rate is the only feature to be altered. For many fetal arrhythmias, echocardiography alone can assess important clinical parameters for diagnosis. Appropriate treatment of the fetus requires awareness of arrhythmia characteristics, mechanisms, and potential associations. Criteria to define fetal bradycardia specific to gestational age are now available and may allow detection of ion channelopathies, which are associated with fetal and neonatal bradycardia. Ectopic beats, once thought to be entirely benign, are now recognized to have important pathologic associations. Fetal tachyarrhythmias can now be defined precisely for mechanism-specific therapy and for subsequent monitoring of response. This article reviews the current and future diagnostic techniques and pharmacologic treatments for fetal arrhythmia.

MicroRNAs and Heart Failure Diagnosis

See related article, pages 1035–1039 Heart disease is the greatest noninfectious health hazard ever to confront the human race. It is the leading cause of death in industrialized nations, and, accordingly, it is responsible for a huge economic burden to society. It is estimated that 5 million Americans have heart failure (HF), a syndrome with mortality of approximately 50% at 5 years.1 Now, evidence indicates that the epidemic of HF is extending to the developing world. The road to advances in the treatment of HF is littered with failures, and many new means of diagnosing and tracking disease progression have disappointed. Therefore, there is an urgent need to identify novel mechanisms, markers, and therapeutic targets in HF pathogenesis. MicroRNAs (miRNAs or miRs) are among the most exciting areas in medicine and science today. MicroRNAs are endogenous, highly conserved, ≈22-nucleotide-long noncoding RNAs that regulate the stability and subsequent translation of nascent mRNA transcripts. Generally, miRs inhibit protein translation and/or promote mRNA degradation by base-pairing with 3′ untranslated regions within a transcript. MicroRNAs were first discovered in 1993 in Caenorhabditis elegans and are known to be critical to early vertebrate development and in an increasing number of basic molecular processes. Over the last few years, miRs have emerged as important mechanisms in human disease, including cardiovascular disease, diabetes, and cancer.2–6 Now, there is burgeoning interest in testing whether miRs could serve as markers for disease progression or prognostication. Indeed, in the cancer literature, strategies are emerging to use miR profiles for diagnosis and risk stratification. Currently, miR profiling is being evaluated in prostate cancer, head and neck squamous cell carcinomas, breast cancer, acute lymphoblastic leukemia, malignant mesothelioma, and other tumors.2,7–10 Most clinical studies to date on miRs have relied on tissue-based measurement of miR abundances, but miRs are …

Identification of Cell Surface Proteins for Antibody-Based Selection of Human Embryonic Stem Cell-Derived Cardiomyocytes

The absence of identified cell surface proteins and corresponding antibodies to most differentiated derivatives of human embryonic stem cells (hESCs) has largely limited selection of specific cell types from mixed cell populations to genetic approaches. Here, we describe the use of mass spectrometry (MS)-based proteomics on cell membrane proteins isolated from hESCs that were differentiated into cardiomyocytes to identify candidate proteins for this particular lineage. Quantitative MS distinguished cardiomyocyte-specific plasma membrane proteins that were highly enriched or detected only in cardiomyocytes derived from hESCs and human fetal hearts compared with a heterogeneous pool of hESC-derived differentiated cells. For several candidates, cardiomyocyte-specific expression and cell surface localization were verified by conventional antibody-based methodologies. Using an antibody against elastin microfibril interfacer 2 (EMILIN2), we demonstrate that cardiomyocytes can be sorted from live cell populations. Besides showing that MS-based membrane proteomics is a powerful tool to identify candidate proteins that allow purification of specific cell lineages from heterogeneous populations, this approach generated a plasma membrane proteome profile suggesting signaling pathways that control cell behavior.

Human fetal heart rate: a unique opportunity to assess the fetal programming hypothesis

AbstractThe study of the human fetus presents several unique challenges. Methods of the measurement and procedures for exploring the functional capability of the fetus coupled with the perceived fragility of the maternal/fetal dyad have been barriers for the study of the human fetus. The studies reported here by Kisilevesky and Hains (2009) and those conducted by others indicate that the psychology of the human fetus is not only important, but also clearly feasible. Kisilevsky and Hains (2009) provide compelling evidence from their own well‐designed studies and the growing number of studies from other investigators that by the middle of the second trimester the human fetus is able to detect ex utero stimulation and by the early third trimester can discriminate and learn associations. The review provides important technical information and physiological rationale for measuring human fetal heart rate as an index of cognition. Other measures of fetal behavior are only briefly discussed. Some, such as MEG and MRI are dismissed as impractical and only feasible near term. Other measures that can be used to assess fetal cognition, such as fetal movement and the elegant studies of fetal movement patterns Salisbury et al. (2005) are not discussed but see articles by Di Pietro, van den Bergh, James, Kawai, Sheridan et al., Huoutilainen, Hata et al. and Emory (this issue). This commentary will focus on the application of the human fetal heart rate measures that both support and broaden the conclusions of Kisilevsky and Hains (2009). Copyright © 2010 John Wiley &amp; Sons, Ltd.

Myocardial bridges of the coronary arteries in the human fetal heart

During the last century, many investigators reported on myocardial bridges in the adult human heart. In the present study, 39 human fetal hearts (the mean gestastional age was 30 weeks) were studied for myocardial bridging, and the results were correlated with adult data. Among the 39 (27 male and 12 female) fetal hearts studied, 26 bridges were observed on 18 fetal hearts (46.2%). Ten of the bridges had one myocardial bridge, whereas double myocardial bridges were observed in eight fetal hearts. The most frequent myocardial bridges were observed on the left anterior descending artery (LAD), which had 13 bridges (50%). Eight (30.7%) myocardial bridges were on the diagonal artery, and on the posterior descending artery there were five (19.3%). Myocardial bridges were not observed on the circumflex artery. The data presented in this study may provide potentially useful information for the preoperative evaluation of the newborn and may have a clinical implication for sudden fetal death.

Human Cardiac Stem Cells

The view of the heart as a static organ implies that myocyte death and formation play a negligible role in cardiac homeostasis. Although stem cells have been unexpectedly identified in several organs, including the brain, kidney, lung, and skeletal muscle, the search for a cardiac stem cell (CSC) has been perceived as a futile effort, given the acknowledged lack of regenerative potential of the myocardium. Nevertheless, in the past several years, the demonstration of myocyte renewal in the normal and diseased heart has revealed a new, dynamic, and lively picture of this organ. Components of the cell cycle machinery and markers of cell replication have been detected in cardiomyocytes. The demonstration that karyokinesis and cytokinesis involve cells expressing contractile proteins has provided evidence that cardiomyocyte division occurs in the adult heart.1 More recently, pulse-chase assays with thymidine analogs,2 lineage tracing protocols,3 and 14C birth dating of cells4 have shown the existence of myocyte turnover, a process that has been found to differ in magnitude according to the methods used for its documentation and quantification. Article see p 2559 Over the years, the heart has provided us with the evidence that solves the critical problem of the origin of cardiomyocytes. At this moment in time, paraphrasing Eugenio Montale, we could say that the human heart is “on the verge of betraying [its] final secret offering the opportunity to uncover…the still point of the world, the link that won't hold, the thread to untangle that will finally lead to the heart of a truth.”5 Newly generated myocytes may derive from division of preexisting parenchymal cells or from activation and differentiation of resident CSCs. Discriminating between these two possibilities is not an easy task. Fate-mapping strategies, which are commonly used to track the origin of cells and …

Three-dimensional reconstruction imaging of the human foetal heart in the first trimester

High-resolution episcopic microscopy (HREM) is a novel method producing high-quality, three-dimensional (3D) images of tissue from a variety of species. We report, for the first time, the use of HREM to create high-resolution 3D reconstructions of the human foetal heart in the first trimester. These models are suitable for a detailed morphological investigation to produce ‘virtual’ images of any section plane and 3D models that can be examined using ‘virtual’ dissection. …

DBTSS provides a tissue specific dynamic view of Transcription Start Sites

DataBase of Transcription Start Sites (DBTSS) is a database which contains precise positional information for transcription start sites (TSSs) of eukaryotic mRNAs. In this update, we included 330 million new tags generated by massively sequencing the 5′-end of oligo-cap selected cDNAs in humans and mice. The tags were collected from normal fetal or adult human tissues, including brain, thymus, liver, kidney and heart, from 6 human cell lines in 21 diverse growth conditions as well as from mouse NIH3T3 cell line: altogether 31 different cell types or culture conditions are represented. This unprecedented increase in depth of data now allows DBTSS to faithfully represent the dynamically changing landscape of TSSs in different cell types and conditions, during development and in the course of evolution. Differential usage of alternative 5′-ends across cell types and conditions can be viewed in a series of new interfaces. Promoter sequence information is now displayed in a comparative genomics viewer where evolutionary turnover of the TSSs can be evaluated. DBTSS can be accessed at http://dbtss.hgc.jp/.

Abstract 5052: Attenuation of Ventricular Remodeling and Improvement of Left Ventricular Systolic Function by Injection of Human Fetal Cardiomyocyte Progenitor Cells After Acute Myocardial Infarction

Introduction: The human cardiomyocyte progenitor cell (hCMPC) is part of a population of stem cells located in the human heart. Isolates of hCMPCs from human fetal hearts showed differentiation into functional cardiomyocytes in vitro. In the present study we investigated the potential of hCMPCs to restore ischemic myocardium and improve left ventricular (LV) function in a myocardial infarction (MI) model in mice. Methods: MI was induced in immune-compromised NOD/scid mice, immediately followed by injection of hCMPCs labeled with eGFP (hCMPC group) or vehicle only (control group). From sham operated mice we obtained reference values. Cardiac performance was measured 2 and 14 days after MI using 9.4 Tesla MRI. LV pressure-volume measurements were performed at day 15 followed by extensive immunohistological analysis. Results: Animals injected with hCMPCs after MI demonstrated a significantly higher LV ejection fraction, a lower LV end-systolic volume and a smaller ô (relaxation time constant), compared to animals from the control group (by 17%, by 22% and by 24% respectively, P&lt;0.05). A trend towards a lower LV end-diastolic volume was also observed, although this did not reach significance (P=0.14). Both the infarct zone and border zone of the hCMCP group showed a significant increase in total blood vessel density (6.67%±0.85% and 9.13%±0.46%) compared to control (3.35%±1.13% and 4.31%±1.08%, P&lt;0.01 in either zone). The infarct and border zone of the hearts injected with hCMPCs also had a diminished collagen type III density (1.07±0.06 and 1.11±0.07), compared to the control group (1.45±0.05 and 1.51±0.08, P&lt;0.01 in either zone). Furthermore, nuclear PCNA expression indicated an increased rate of mitosis in the infarct (37.76%±2.23%) and border zone (48.84%±2.07%) compared to the infarct (25.48%±4.83%, P&lt;0.01) and border zone (32.03%±1.03%, P&lt;0.01) of the control group. Conclusions: Fetal hCMPCs engraft into infarcted myocardium where they improve LV systolic function and attenuate ventricular remodeling. Increased blood vessel density, elevated mitosis rate and decreased collagen III deposition may be involved in this process. These results indicate that hCMPCs are promising candidates for cell-based therapy.

Human cardiomyocyte progenitor cell-derived cardiomyocytes display a maturated electrical phenotype

Cardiomyocyte progenitor cells (CMPCs) can be isolated from the human heart and differentiated into cardiomyocytes in vitro. A comprehensive assessment of their electrical phenotype upon differentiation is essential to predict potential future applications of this cell source. CMPCs isolated from human fetal heart were differentiated in vitro and examined using immunohistochemistry, Western blotting, RT-PCR, voltage clamp and current clamp techniques. Differentiated cultures presented up to 95% α-actinin positive cardiomyocytes. Adherens junction and desmosomal proteins β-catenin, N-cadherin, desmin and plakophilin2 were upregulated. Expression levels of cardiac connexins were not affected by differentiation, however Cx43 phosphorylation was increased upon differentiation, accompanied by translocation of connexins to the cell border. RT-PCR analysis demonstrated upregulation of all major cardiac ion channel constituents during differentiation. Patch clamp experiments showed that cardiomyocytes had a stable resting membrane potential of − 73.4 ± 1.8 mV. Infusion of 1 mM BaCl 2 resulted in depolarization to − 59.9 ± 2.8 mV, indicating I K1 channel activity. Subsequent voltage clamp experiments confirmed presence of near mature I Na, I Ca,L and I K1 current densities. Infusion of the I Kr blocker Almokalant caused prolongation of the action potential by 40%. Differentiated monolayers were not spontaneously contracting in the absence of serum, but responded to field stimulation, displaying adult ventricular-like action potentials. Human fetal CMPC-derived cardiomyocytes have a homogenous and rather mature electrical phenotype that benefits to in vitro physiology and pharmacology. In the context of cardiac repair, their properties may translate into a reduced pro-arrhythmic risk and enhanced electrical integration upon transplantation.

Comparison of human post-embryonic, multipotent stem cells derived from various tissues

Multipotent stem cells were isolated from human fetal heart, liver, muscle, lung, derma, kidney, and adipose tissue, and then analyzed for their characteristics and function. Cells with characteristics similar to bone marrow-derived post-embryonic multipotent stem cells can be selected and cultured from tissues other than bone marrow. This may then help explain the "stem cell plasticity" found in multiple human tissues.

N004 Isolation of cardiac precursor cells from the human fetal heart

To identify a suitable source of human cardiac precursor cells (CPC) for replacement cell therapies, we established the conditions to isolate precursors from the human fetal heart. Ventricles were collected from donation following voluntary pregnancy termination at 12 weeks of gestation. Non-myocyte cells were isolated, and expanded in vitro. CPC were identified using immunostaining for Nkx2.5, Flk1 and Isl1, and by measuring the expression levels of these markers by real-time PCR. Proliferating cells demonstrated Nkx2.5 staining and no α-actinin expression. A significant fraction of Nkx2.5+ cells expressed Flk1. A few Nkx2.5+ cells were also Isl1+ whereas no Flk1+ cells expressed this marker. The capacity of expanded cells to produce differentiated cardiomyocytes, smooth muscle cells and endothelial cells was then tested by switching the culture to a differentiation serum-free medium. Differentiation into cardiomyocytes, smooth muscle and endothelial cells was evaluated by immunostaining for α-actinin, sm-MHC and CD31 respectively. In addition, expression of cardiac-specific (Nkx2.5, α-MHC, β-MHC), smooth muscle-specific (sm-MHC) and endothelial-specific (CD31) genes was measured using real-time PCR. Evidence for cardiogenic differentiation in the culture is supported by the significant increase in α-actinin+ cells (1 % and 20 % under expansion and differentiation conditions respectively) as well as by the upregulation of cardiac marker expression. Differentiation into smooth muscle cell type was also dramatically stimulated (0 % and 4 % respectively). Accordingly, sm-MHC expression was 25-fold increased. In contrast, no differentiation into endothelial cells was detected under these conditions. The engraftment and differentiation capacity of GFP-labeled CPC were tested in vivo by transfer into the heart of SCID mice after myocardial infarction. Seven days thereafter, engrafted cells were readily detected and demonstrated cardiac-commitment as shown by Nkx2.5 staining. At this stage, no differentiation into cardiomyocytes could be observed.

Expression of the congenital heart disease 5/tryptophan rich basic protein homologue gene during heart development in Medaka fish, Oryzias latipes

The congenital heart disease 5 (CHD5)/tryptophan rich basic protein (WRB) is a protein containing a tryptophan-rich carboxy-terminal region, which was discovered in the human fetal heart. In humans, this CHD5/WRB is located between the markers ACTL5-D21S268 within the Down syndrome (DS) Region-2 at chromosome 21. Congenital heart disease is commonly linked to DS patients. The functions of this gene product are unknown. To identify the functions of CHD5/WRB in heart formation during embryogenesis, the medaka CHD5 cDNA (mCHD5) was isolated and its gene expression pattern and the localization of its gene product were investigated. The obtained mCHD5 belongs to the CHD5 superfamily, whose members include coiled-coil proteins. The mCHD5 gene was found to be expressed in the developing heart after stage 28 at which the chamber (ventricle and atrium) differentiation in the heart tube is initiated in the embryo. Its gene product was also detected in the developing heart at embryonic stage 28 and 35. Knocking-down of mCHD5 function caused severe cardiac disorder, including abnormal chamber differentiation, abnormal looping and ocular abnormality such as Cyclops. Our results provide the mCHD5 gene expression pattern as well as its physiological role during heart formation in a vertebrate model system.

MicroRNA Microarray Expression Profiling in Human Myocardial Infarction

MicroRNAs (miRNAs), small non-coding RNA molecules, are negative regulators of gene expression. Recent studies have indicated their role in various forms of cardiovascular disease. In spite of the number of miRNA microarray analyses performed, little is known about the genome-wide miRNA expression pattern in human myocardial infarction (MI). Using miRNA microarrays and bioinformatic analysis, miRNA expression was analyzed on human MI and foetal hearts compared to healthy adult hearts, to determine whether there is any similar expression pattern between MI and foetal hearts, and to identified miRNAs that have not previously been described as dysregulated in cardiovascular diseases. Of 719 miRNAs analyzed, ∼ 50% were expressed in human hearts, 77 miRNAs were absent from all tested tissues and 57 were confidently dysregulated in at least one tested group. Some expression patterns appeared to be similar in MI and foetal hearts. Bioinformatic analysis revealed 10 miRNAs as dysregulated in MI not yet related to cardiovascular disease, and 5 miRNAs previously described only in animal models of cardiovascular diseases. Finally, qRT-PCR analysis confirmed dysregulation of 7 miRNAs,miR-150, miR-186, miR-210, miR-451, and muscle-specific, miR-1 and miR-133a/b; all of these are believed to be involved in various physiological and pathological processes.