ABSTRACT
Cilia are protruding cell structures on the cell surface and are found in almost every type of cell.According to the different structures and quantity of tubulins,cilia can be divided into two categories:motor cilia and sensory cilia.Sensory cilia are also called non-motor cilia and primary cilia,due to the composition and number of tubulins.They are closely related to the development of internal organs and many human physiological activities.Recent studies have demonstrated that cilia are involved in regulating the formation of left and right symmetry of the heart structure,and eventually the heart develops into the left-right asymmetry structures.Since congenital heart diseases(CHD)are characterized by abnormalities in the spatial structure of the heart chamber and outflow tract,cilia may play an important role in the pathogenesis of CHD.Cilia,mainly through ciliary transduction signal pathways,regulate both the formation of left and right asymmetrical structures and the polarity and the migration of cells.Therefore,a clear understanding of the regulation mechanism of ciliary signaling pathway on heart development can provide new therapeutic targets and new ideas for the clinical treatment of CHD and may offer new target genes for prenatal screening of CHD.This article summarizes recent advances in the role of cilia in heart development and CHD pathogenesis and its mechanisms.
ABSTRACT
GATA6 transcription factor belongs to the GATA family and contains 2 conserved zinc ifnger DNA binding domains. GATA6 not only presents in embryonic tissues but also found in heart, lung and pancreas and is essential for the maintenance of their function.The present review focuses on the critical roles of GATA6 in heart development and atrial septal defect to provide theoretical basis for diagnosis and treatment of atrial septal defect.
ABSTRACT
Objective To investigate the functional role of a soluble secretion factor midkine-a in the process of zebrafish embryonic heart development .Methods Whole-mount in situ hybridization was performed to detect whether midkine-a is expressed in the embryonic heart .In the transgenic embryonic heart of Tg ( pmidkine-a:EGFP) , the expres-sion of EGFP in the heart was monitored .Multiple heat shock treatments were applied to Tg (phsp:midkine-a:EGFP) em-bryos in order to overexpress midkine-a, and the phenotype of the heart was observed .The heterozygous Tg ( phsp:mid-kine-a:EGFP) fish were crossed with homozygous Tg (pcmlc2:dsRed) fish, which specifically expresses RFP in the nucle-oli of embryonic cardiomyocytes to facilitate myocyte number counting .To get Tg ( phsp:midkine-a:EGFP/pcmlc2:dsRed)embryos, and the total number of cardiomyocytes in their heart was counted and compared with the controls when the heat shock induced overexpression of midkine-a.Morphonino knocked out of midkine-a was performed to observe the heart phe-notype.Results Midkine-a was expressed in the zebrafish embryonic heart during development .Overexpression of mid-kine-a led to a smaller heart and reduced total number of cardiomyoctes in a single heart , which might be associated with the smaller heart phenotype .Morphonilo knocked out of midkine-a had no effect upon the heart development .Conclusions Midkine-a impedes zebrafish embryonic heart growth by limiting its cardiomyocyte pool .
ABSTRACT
Objective To investigate the effects of oral folic acid supplementation on the expressions of heart devel-opment-related proteins GATA4 and Nkx2 . 5 of offspring in the rat models of maternal hyperglycemia during preg-nancy. Methods Forty Sprague-Dawly( SD) rats in pregnancy were randomly divided into 5 groups:control group, models group, FA3rd group, FA7th group and FA15th group. Except for the control group, maternal hyperglycemi-a was induced by a single intraperitoneal injection of streptozotocin (38 mg/kg) in SD rats of four other groups on the first day of pregnancy. And group FA3rd, FA7th, FA15th were intragastriced with folic acid (0. 8 mg/kg per day) from day 3,7,and 15 of pregnancy respectively until the end of the pregnancy. The hearts of neonates were taken on the 21st day of pregnancy and the heart tissues with haematoxylin and eosin staining were observed. The expressions of GATA4 and Nkx2. 5 proteins were detected by immunohistochemistry and Western blot. Results The blood glucose level of pregant rats intervened by streptozotocin was significantly increased(P<0. 05),and in a part of their offspring,the cardiac injury was detected. GATA4 protein was expressed in atria,ventricles, interven-tricular septum and valvular tissues. Nkx2. 5 protein was expressed in atria, ventricles and interventricular septum, while it was not expressed obviously in valvular tissues. The expression levels of GATA4 and Nkx2. 5 were de-creased in the groups intervened by streptozotocin compared with the control group(P<0. 05). The expression lev-els of GATA4 and Nkx2. 5 in FA3rd group and FA7th group were higher than that of the models group(P<0. 05). Compared with FA7th group, the expression of GATA4 and Nkx2. 5 in FA3rd group increased greatly(P<0. 05). However, it showed no significant difference between the models group and FA15th group. Conclusion Maternal hyperglycemia during pregnancy may result in offspring’ s cardiac injury and decrease their expressions of heart de-velopment-related protein GATA4 and Nkx2. 5 at the same time. Folic acid supplementation may increase the ex-pressions of GATA4 and Nkx2. 5 protein and has a protective effect on offspring’s myocardial development of mater-nal hyperglycemia in pregnancy.
ABSTRACT
Congenital heart disease is caused by abnormal embryonic heart development.According to the research findings of developmental biology,different heart cells must be strictly regulated to ensure proper cell location and development.In the process of heart development,transcription factors play an important role in the regulation of gene expression.Zinc finger transcription factor GATA-6,an early indicator of myocardial cell development,is currently regarded as main candidate gene involved in the pathogenesis of congenital heart disease.GATA-6 gene mutations lead to changes in transcriptional activity of the gene product,which together with other relevant factors may play a role in the pathogenesis of congenital heart disease.
ABSTRACT
Objective To explore the potential role of HOXA3 gene in children with tetralogy of fallot (TOF) by detection the expression of HOXA3 mRNA and protein levels,as well as the apoptotic cardiomyocytes in the developing heart tissues.Methods Twenty-two surgical samples from sporadic cases of TOF determined by prenatal color Doppler ultrasound and autopsy [gestational age(25.67 ± 7.68) weeks,TOF group] were examined with quantitative real-time PCR and Western blot to evaluate the expression of HOXA3 gene.Twelve age-matched autopsies without heart structural abnormalities [gestational age (26.55 ± 6.36) weeks,control group] were also included.Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling(TUNEL) assay was performed to clarify the apoptosis of cardiomyocytes.The difference between the 2 groups and the correlation analysis of HOXA3 level and the apoptotic cardiomyocytes were performed with SPSS 13.0 software.Results Compared with control group,HOXA3 mRNA expression of the outflow tract of the right ventricle from the TOF group was significantly reduced(P ＜ O.01).Western blot also confirmed that the HOXA3 protein was accordingly reduced(P ＜0.01).The proportion of apoptotic cardiomyocytes in samples of TOF group was significantly greater than that of control group (P ＜ 0.01).The proportion of apoptotic cells was strongly correlated with the mRNA and protein expression of HOXA3 (r =-0.566,-0.759,all P ＜ 0.01).Conclusions Reduction of HOXA3 gene expression and the increase of apoptotic cardiomyocytes at the crucial stage during heart development may play a potential role in the onset of TOF.
ABSTRACT
Objective To investigate the changes of gene expression in the cardiac outflow tract (OFT) in Cx43 knockout (Cx43-/-) mouse embryos, and to elucidate the genes involved in the myocardialization of proximal cardiae outflow tract septum. Methods The cDNA was retrotranscripted from RNA, which extracted from OFT tissues of both Cx43-/- and Cx43 wild type (Cx43+/+) mouse embryos on embryonic day (ED) 14.5. The biotin-labeled cRNA derived from the transcription of cDNA was fragmented as probes. The probes were hybridized with Affymetrix Mouse Genome 430 2.0 Array. Gene Array Scanner was used to screen the signals of hybridization, and the expression of genes was detected. Results Among the differentially expressed genes, there were 143 upregulated and 235 downregulated in Cx43 knockout OFT tissue compared with those in Cx43+/+ heart. Functions of proteins encoded by the altered genes encompassed all functional categories, with the largest percentage in genes involved in signaling pathways such as regulation of transcription, cell cycle, etc. Among the differentially expressed genes in the Cx43-/- heart, some were related with TGFβ/BMP signaling pathway, and Ssr1, Ptk2 and Bmp6 were related with conotruncal defects. These genes were verified by Real-time PCR, and the result was consistent with that of microarray (P<0.05).Conclusions Scaned by Gene Array and verified by Real-time PCR, genes related with TGFβ/BMP signaling pathway, and Ssr1, Ptk2 and Bmp6 were differentially expressed in ED 14.5 Cx43-/- OFT tissue, which may be involved in the myocardialization of proximal cardiac outflow tract septum.
ABSTRACT
Objective:Cardiogenesis is a precise process controlled by sequential gene regulatory steps.Heart-specific transcription factors (TFs)GATA4,Nkx2.5,MEF2C and Tbx5 play critical roles in controlling heart development.But the genetic basis for the temporal expression of genes during heart development still remains unclear.Substantial studies displayed gene regulation partly attributes to histone acetylation.However,the functions of individual histone acetyltransferases (HATs)in specific developmental transcription programs are not well elucidated.p300,a histone acetyltransferase and coactivator,plays key role in many physiological processes,moreover our previous study suggests that expression of p300 is developmentally regulated during mouse cardiogenesis,but the underlying molecular mechanism remains elusive.Methods:The whole hearts from embryonic mice on embryonic days (E)10.5 and 16.5 were collected accordingly,and then total RNA was extracted.Heart-specific TFs GATA4,Nkx2.5,MEF2C and Tbx5 mRNA from mouse myocardium at differential embryonic days during cardiac development were analyzed by quantitative (Q)-PCR.The levels of histone H3 acetylation on these heart-specific TFs promoter and transcription factor binding sites of p300 to these genes were identified by chromatin immunoprecipitation assays (ChIP).Results:The present study furnishes a comparative temporal expression map of cardiac transcriptional factors,during murine heart development (E10.5 and E16.5).The mRNA levels of these genes present dynamic change.On E10.5,the expressions of GATA4 and MEF2C were remarkable lower than those on E16.5 (P
ABSTRACT
Objective To investigate the spatiotemporal expression patterns and the relationship of α-sarcomeric actin(α-SCA) ,α-smooth muscle actin(α-SMA) and intermediate filament protein desmin with the maturation of the prenatal and the neonatal mouse hearts. Methods Serial sections of the embryo mouse and the neonatal mouse hearts were immunostained with antibodies against α-SCA, α-SMA and desmin. Results Ventricle and outflow tract of embryonic day(ED) 9 heart showed stronger expression of α-SCA and α-SMA, but desmin expression was lower. In the atrium, the expressions of α-SCA and α-SMA were restricted to the dorsal and ventral walls. In the sinus venosus, only a few weakly stained α-SCA positive cells were detected. No desmin expression was found in the atrium and sinus venosus. The expressions of α-SCA, α-SMA and desmin were increased to their highest level at ED 12. The higher expression of α-SCA remained to the postnatal stages. After ED 12, the expressions of α-SMA and desmin gradually decreased in different parts of the heart, but their expressions in the right ventricle persisted longer. After birth,desmin expression was mainly concentrated in the Z lines of I bands and intercalated disks. Conclusion The presence of spatiotemporal differences in the expression of α-SMA and desmin reveals regional differences in cardiomyocyte maturation in various parts of the embryonic mouse heart. The right ventricle shows a relatively slow pace of maturation. The α-SMA may contribute to a peristaltoid contraction pattern of the embryonic myocardium with a slow shortening speed, and a relatively higher level of desmin is required for the maturation of the sarcomere.
ABSTRACT
El propósito de esta revisión es analizar las diferentes rutas metabólicas utilizadas por el corazón en momentos del desarrollo y situaciones como la hipoxia y la enfermedad, para tratar de comprenderlas y utilizarlas para restablecer las condiciones normales en células que se encuentran comprometidas durante un infarto.
We describe different metabolic states of the heart, during developmental stages, hypoxia and illness, to understand and use them to try to reestablish the normal conditions. (Arch Cardiol Mex 2003; 73:218-229).
Subject(s)
Adult , Animals , Humans , Myocardium/metabolism , Biological Evolution , Cell Hypoxia/physiology , Ischemia/metabolismABSTRACT
Objective: To investigate the expression of the transcription factor GATA-4 in human heart development.Methods: Immunohistochemistry was used to detect the expression of GATA-4 in 45 normal human embryonic hearts of 6-23 gestational weeks.Results: In the early stage of the fetal heart morphogenesis,we observed no GATA-4 expression in the ventricle,weak expression in the atria and relatively high expression in the trabecular nets.With the heart development,the GATA-4 expression was enhanced in the atria,ventricle,trabecular nets and atrial-ventricular valves,as well as in the muscular and membranous interventricular septum,the highest in each part of the heart.Conclusion: The transcription factor GATA-4 plays an important role in human heart development.
ABSTRACT
A total of 23 human fetal hearts from 18 to 40 weeks of gestation were provided for histologic and morphometric studies. The fetuses were the products of spontaneous or artificial abortions and were found to have no congential anomalies or associated lesions at autopsy. Maxima thickness of the left anterior, left lateral, left posterior, right anterior, right lateral, right posterior ventricular wall, and of the interventricular septal wall were measured and the left / right wall thickness ratio was calculated. The cross-sectional area of each ventricle parallel to the base of the heart at about 3-5mm below from the origin of the aorta was measured under drawing attachment-equipped light microscope with the application of point counting or cut-and-weigh method. Data were analyzed by the Anderson-ell ABSTAT dBASE ll statistical package program. The ventricular wall consisted of endocardium, myocardium and epicardium. The myocardium showed epithelial character by stratification of barrel-shaped myocardial cells, but the epithelial character progressively changed to as in adult myocardial tissue from the myocardial area close to the epicardium with increasing fetal age. However, any significant histologic difference between the left and the right ventricular wall at the same fetal age was not found. The growth pattern of both ventricular wall, the interventricular septal wall, and of the cross sectional area were linear (p0.1).
Subject(s)
Adult , Humans , Pregnancy , Aorta , Autopsy , Endocardium , Fetal Heart , Fetus , Gestational Age , Heart , Heart Ventricles , Methods , Myocardium , PericardiumABSTRACT
Objective To detect the expression of nesprin-1 gene mRNA and protein and to localize the sub-cellular protein during the development of mouse heart.Methods Samples of embryonic heart tissue were collected from postnatal and adult mice on embryo 12.5 days(E12.5),E14.5,E16.5,and E18.5,respectively.Expression levels of nesprin-1 mRNA and protein and the protein sub-cellular location in samples of embryonic heart tissue from mice were detected by reverse transcriptase PCR,Western blot analysis and immunofluorescence at different time points.Results The expression level of nesprin-1 mRNA and protein in samples of embryonic heart tissue from postnatal and adult mice was measured on E12.5,E16.5 and E18.5,respectively,which increased with the development of mouse heart,reached it peak on E16.5 and E18.5.The lowest expression level of nesprin-1 mRNA and protein was found in adult mice.Immunofluorescence showed that nesprin-1 was distributed in nuclear envelope and in spaces around the nuclei.Conclusion nesprin-1 is dynamically expressed during the development of mouse heart,and highly expressed in the mature period of cardiac conduction system and cardiac muscle cells,indicating that it plays an important role in the development of cardiac conduction system and cardiac muscle cells.
ABSTRACT
Objective To investigate the spatiotemporal expression patterns and the relationship of ?-sarcomeric actin(?-SCA),?-smooth muscle actin(?-SMA) and intermediate filament protein desmin with the maturation of the prenatal and the neonatal mouse hearts.Methods Serial sections of the embryo mouse and the neonatal mouse hearts were immunostained with antibodies against ?-SCA,?-SMA and desmin.Results Ventricle and outflow tract of embryonic day(ED) 9 heart showed stronger expression of ?-SCA and ?-SMA,but desmin expression was lower.In the atrium,the expressions of ?-SCA and ?-SMA were restricted to the dorsal and ventral walls.In the sinus venosus,only a few weakly stained ?-SCA positive cells were detected.No desmin expression was found in the atrium and sinus venosus.The expressions of ?-SCA,?-SMA and desmin were increased to their highest level at ED 12.The higher expression of ?-SCA remained to the postnatal stages.After ED 12,the expressions of ?-SMA and desmin gradually decreased in different parts of the heart,but their expressions in the right ventricle persisted longer.After birth,desmin expression was mainly concentrated in the Z lines of I bands and intercalated disks.Conclusion The presence of spatiotemporal differences in the expression of ?-SMA and desmin reveals regional differences in cardiomyocyte maturation in various parts of the embryonic mouse heart.The right ventricle shows a relatively slow pace of maturation.The ?-SMA may contribute to a peristaltoid contraction pattern of the embryonic myocardium with a slow shortening speed,and a relatively higher level of desmin is required for the maturation of the sarcomere.