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Hexafluoropropylene oxide trimer acid,a perfluorooctanoic acid alternative,induces cardiovascular toxicity in zebrafish embryos

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Journal of Environmental Sciences 2024年第5期139卷 460-472页

作者： Sujie Sun Li Zhang Xue Li Lu Zang Ling Huang Junquan Zeng Zigang Cao Xinjun Liao Zilin Zhong Huiqiang Lu Jianjun Chen Jiangxi Engineering Laboratory of Zebrafish Modeling and Drug Screening for Human Diseases Jiangxi Key Laboratory of Developmental Biology of OrgansCenter for Clinical Research Center of the Affiliated Hospital of Jinggangshan UniversityJi’an 343009China Translational Research Institute of Brain and Brain-like Intelligence Shanghai Key Laboratory of Anesthesiology and Brain Functional ModulationDepartment of PediatricsShanghai Fourth People’s HospitalSchool of MedicineTongji UniversityShanghai 200434China State Environmental Protection Key Laboratory of Environmental Health Impact Assessment of Emerging Contaminants School of Environmental Sciences and EngineeringShanghai Jiao Tong UniversityShanghai 200240China Department of Interventional and Vascular Surgery Affiliated Hospital of Jinggangshan UniversityJi’an 343009China Department of Internal Medicine and Hematology Affiliated Hospital of Jinggangshan UniversityJi’an 343009China

As an increasingly used alternative to perfluorooctanoic acid(PFOA),hexafluoropropylene oxide trimer acid(HFPO-TA)has been widely detected in global water ***,little is known regarding its toxic effects on cardiovascular ***,zebrafish embryos were treated with egg water containing 0,60,120,or 240 mg/L *** showed that HFPO-TA treatment led to a significant reduction in both larval survival percentage and heart ***,HFPO-TA exposure caused severe pericardial edema and elongation of the sinus venous to bulbus arteriosus distance(SV-BA)in Tg(myl7:GFP)transgenic larvae,disrupting the expression of genes involved in heart development and thus causing abnormal heart *** sprouting angiogenesis was observed in the 120 and 240 mg/L exposed Tg(fli:GFP)transgenic ***-TA treatment also impacted the mRNA levels of genes involved in the vascular endothelial growth factor(VEGF)pathway and embryonic vascular ***-TA exposure significantly decreased erythrocyte number in Tg(gata1:DsRed)transgenic embryos and influenced gene expression associated with the heme metabolism ***-TA also induced oxidative stress and altered the transcriptional levels of genes related to cell cycle and apoptosis,inhibiting cell proliferation while promoting ***,HFPO-TA exposure may induce abnormal development of the cardiovascular and hematopoietic systems in zebrafish embryos,suggesting it may not be a suitable or safe alternative for PFOA.

关键词： Hexafluoropropylene oxide trimer acid heart development Vascular development Hemopoiesis Zebrafish embryos

The role of cellular senescence in cardiac development,regeneration and diseases

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South China Journal of Cardiology 2022年第1期23卷 19-26,32页

作者：严磊刘南波朱烁基朱平张辉 School of Life Science and Technology ShanghaiTech UniversityShanghai 201210China Guangdong Cardiovascular Institute Guangdong Provincial People's HospitalGuangdong Academy of Medical SciencesGuangzhouGuangdong 510100China Guangdong Provincial Key Laboratory of Pathogenesis Targeted Prevention and Treatment of Heart Disease

Background Cellular senescence,an irreversible state of cell-cycle arrest triggered by multiple stress factors,plays a key role in organ development and wound *** senescent cells also promote tissue inflammation and involve in various diseases including myocardial infarction,atherosclerosis,diabetes and nonalcoholic *** the mechanism and consequences of cellular senescence is crucial to develop new therapies for ***,we describe the characteristics of senescent cells and involvement of senescent cardiac cells in heart development,regeneration and *** summarize the work in this area and provide directions and clues for future studies.

关键词： cellular senescence stress factors heart development heart regeneration heart diseases

Continuous live imaging reveals a subtle pathological alteration with cell behaviors in congenital heart malformation

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Fundamental Research 2022年第1期2卷 14-22页

作者： Xin Li Yanzhu Yue Youdong Zhang Yuanhui Liao Qianhao Wang Yunkun Bian Jie Na Aibin He Beijing Key Laboratory of Cardiometabolic Molecular Medicine Institute of Molecular MedicineCollege of Future TechnologyPeking-Tsinghua Center for Life SciencesPeking UniversityBeijing 100871China School of Software and Microelectronics Peking UniversityBeijing 100871China Centre for Stem Cell Biology and Regenerative Medicine School of MedicineTsinghua UniversityBeijing 100084China

To form fully functional four-chambered structure,mammalian heart development undergoes a transient finger-shaped trabeculae,crucial for efficient contraction and exchange for gas and *** its developmental origin and direct relevance to congenital heart disease has been studied extensively,the time-resolved cellular mechanism underlying hypotrabeculation remains ***,we employed in toto live imaging and reconstructed the holistic cell lineages and cellular behavior landscape of control and hypotrabeculed hearts of mouse embryos from E9.5 for up to 24 *** to control,hypotrabeculation in ErbB2 mutants arose mainly through dual mechanisms:both reduced proliferation of trabecular cardiomyocytes from early cell fate segregation and markedly impaired oriented cell division and *** examination of mosaic mutant hearts confirmed alterations in cellular behaviors in a cell autonomous ***,our work offers a framework for continuous live imaging and digital cell lineage analysis to better understand subtle pathological alterations in congenital heart disease.

关键词： Live imaging heart development Cell behaviors Trabeculation Congenital heart disease

Global DNA methylation and transcriptional analyses of human ESC-derived cardiomyocytes

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Protein & Cell 2014年第1期5卷 59-68页

作者： Ying Gut Guang-Hui Liu Nongluk Plongthongkum' Christopher Benner Fei Yi Jing Qu Keiichiro Suzuki Jiping Yang Weiqi Zhang Mo Li Nuria Montserrat Isaac Crespo Antonio del Sol Concepcion Rodriguez Esteban Kun Zhang Juan Carlos Izpisua Belmonte Gene Expression Laboratory Salk Institute for Biological Studies 10010 North Torrey Pines Road La Jolla CA 92037 USA National Laboratory of Biomacromolecules institute of Biophysics Chinese Academy of Sciences Beijing 100101 China ' State key Laboratory of Drug Research Shanghai Institute of Materia Medica Chinese Academy of Sciences Shanghai 201203 China Department of Bioengineering University of California at San Diego La Jolla CA 92093 USA center of Regenerative Medicine in Barcelona Dr. Aiguader 88 08003 Barcelona Spain Biomedical Research Networking Center in Bioengineering Biomaterials and Nanomedicine (CIBER-BBN) Poeta MarianoEsquillor s/n 50018 Sargossa Spain Luxembourg Centre for Systems Biomedicine (LCSB) University of Luxembourg Walferdange Luxembourg

With defined culture protocol, human embryonic stem cells （hESCs） are able to generate cardiomyocytes in vitro, therefore providing a great model for human heart development, and holding great potential for car- diac disease therapies. In this study, we successfully generated a highly pure population of human cardio- myocytes （hCMs）（〉95% cTnT＋） from hESC line, which enabled us to identify and characterize an hCM-specific signature, at both the gene expression and DNA meth- ylation levels. Gene functional association network and gene-disease network analyses of these hCM-enriched genes provide new insights into the mechanisms of hCM transcriptional regulation, and stand as an informative and rich resource for investigating cardiac gene func- tions and disease mechanisms. Moreover, we show that cardiac-structural genes and cardiac-transcription fac- tors have distinct epigenetic mechanisms to regulate their gene expression, providing a better understandingof how the epigenetic machinery coordinates to regulate gene expression in different cell types.

关键词： human cardiomyocyte DNA methylation,microarray heart development

Microarray-bioinformatics analysis of altered genomic expression profiles between human fetal and infant myocardium

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Chinese Medical Journal 2008年第14期121卷 1257-1264页

作者： KONG Bo LIU Ying-long LU Xiao-dong Pediatric Cardiac Center Cardiovascular Institute and Fuwai Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100037 China

Background The physiological differences between fetal and postnatal heart have been well characterized at the cellular level. However, the genetic mechanisms governing and regulating these differences have only been partially elucidated. Elucidation of the differentially expressed genes profile before and after birth has never been systematically proposed and analyzed. Methods The human oligonucleotide microarray and bioinformatics analysis approaches were applied to isolate and classify the differentially expressed genes between fetal and infant cardiac tissue samples. Quantitative real-time PCR was used to confirm the results from the microarray. Results Two hundred and forty-two differentially expressed genes were discovered and classified into 13 categories, including genes related to energy metabolism, myocyte hyperplasia, development, muscle contraction, protein synthesis and degradation, extracellular matrix components, transcription factors, apoptosis, signal pathway molecules, organelle organization and several other biological processes. Moreover, 95 genes were identified which had not previously been reported to be expressed in the heart. Conclusions The study systematically analyzed the alteration of the gene expression profile between the human fetal and infant myocardium. A number of genes were discovered which had not been reported to be expressed in the heart. The data provided insight into the physical development mechanisms of the heart before and after birth.

关键词： oligonucleotide microarrays bioinformatics gene ontology heart development

Mitogen-activated protein kinase signal pathways play an important role in right ventricular hypertrophy of tetralogy of Fallot

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Chinese Medical Journal 2012年第13期125卷 2243-2249页

作者： ZHANG Hong-shan WU Qing-yu XU Ming ZHOU Yu-xiang SHUI Chao-xiang heart Center First Hospital of Tsinghua University Beijing100016 China Medical College of Tsinghua University Beijing 100084 China Capital Biochip Corporation Beijing 100084 China

Background Tetralogy of Fallot （TOF） is the most common malformation of children with an incidence of approximately 10% of congenital heart disease patients. There can be a wide spectrum to the severity of the anatomic defects, which include ventricular septal defect, aortic override, right ventricular outflow tract obstruction, and right ventricular hypertrophy. We examined the relationship between right ventricular hypertrophy in patients with TOF and the gene expression of factors in the mitogen-activated protein kinase （MAPK） signal pathway. Methods To gain insight into the characteristic gene（s） involved in molecular mechanisms of right ventricular hypertrophy in TOF, differential mRNA and micro RNA expression profiles were assessed using expression-based micro array technology on right ventricular biopsies from young TOF patients who underwent primary correction and on normal heart tissue. We then analyzed the gene expression of the MAPK signal pathway using reverse transcription-polymerase chain reaction （RT-PCR） in normals and TOF patients. Results Using the micro RNA chip V3.0 and human whole genome oligonucleotide microarray VI.0 to detect the gene expression, we found 1068 genes showing altered expression of at least two-fold in TOF patients compared to the normal hearts, and 47 micro RNAs that showed a significant difference of at least two-fold in TOF patients. We then analyzed these mRNAs and micro RNAs by target gene predicting software Microcosm Targets version 5.0, and determined those mRNA highly relevant to the right ventricular hypertrophy by RT-PCR method. There were obvious differences in the gene expression of factors in the MAPK signal pathway when using RT-PCR, which was consistent to the results of the cDNA *** The upregulation of genes in the MAPK signal pathway may be the key events that contribute to right ventricular hypertrophy and stunted angiogenesis in patients with TOF.

关键词： tetralogy of Fallot gene expression heart development mitogen-activated protein kinases microarray micro RNA mRNA Conclusion The upregulation of genes in the MAPK signal pathway may be the key events that contribute to rightventricular hypertrophy and stunted angiogenesis in patients with TOF.

PAQR family members in cell signaling and development

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PAQR family members in cell signaling and development

急性心肌缺血和心脏发育过程中双孔钾通道TREK-1的表达研究（英文）

第三届细胞结构与功能的信号基础研讨会

作者：陈雁中国科学院上海生命科学学院营养研究所

Ras plays a pivotal role in many cellular activities and subcellular compartmentation of Ras as well as its downstream signaling components controls the information flow and output in the context of stimulus and cell ***,how Ras signaling is modulated by subcellular compartmentation at the Golgi apparatus as well as its physiological significance are largely *** we report a mode of spatial regulation of Ras signaling by two highly homologous proteins RasTG1 and RasTG2(Ras Trapping to Golgi 1 and 2) of the PAQR *** RasTGs are membrane proteins specifically localized at the Golgi *** interacts with HRas and NRas and mobilizes them onto the Golgi apparatus,in which Ras is activated in situ,leading to activation of MEK,ERK,and other downstream targets. RasTG also engages a guanine nucleotide exchange protein RasGRP1 onto the Golgi, contributing to the activation of Ras at the *** zebrafish,knockdown of RasTG2 leads to defects in the development of atrioventricular canal and formation of heart ***,MEK inhibitors and a dominant negative HRas can mimic RasTG2 knockdown in inducing cardiac developmental *** active HRas is able to rescue the cardiac defects caused by RasTG2 *** together,these data uncover a new paradigm of Ras signaling,whereby RasTG serves as an organelle-restricted protein that tethers Ras to the Golgi apparatus and such spatial regulation of Ras plays an important role in cardiac valve development.

关键词： Cell signaling Ras MAPK heart development

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急性心肌缺血和心脏发育过程中双孔钾通道TREK-1的表达研究（英文...