title: MicroRNA-34a targets regulator of calcineurin 1 to modulate endothelial inflammation after fetal cardiac bypass in goat placenta.
abstract: Placental dysfunction characterized by vascular endothelial inflammation is one of the most notable responses to fetal cardiac bypass. Regulator of calcineurin 1 (RCAN1) is an important regulator of inflammatory responses. MicroRNAs (miRNAs) are essential post-transcriptional modulators of gene expression, and miRNA-34a (miR-34a) was showed to activate vascular endothelial inflammation. We hypothesized that miR-34a may be a key regulator of placental dysfunction after fetal cardiac bypass.
  
  
  
  We evaluated miRNA expression in goat placentas via small RNA sequencing, quantitative real-time polymerase chain reaction (qRT-PCR) and in situ hybridization. Expression of miRNA target genes was determined via bioinformatics analyses and dual luciferase reporter assays. Furthermore, human umbilical vein endothelial cells (HUVECs) were transfected with miR-34a or a control sequence. The RCAN1, nuclear factor of activated T-cells (NFATC1) and nuclear factor kappa-B (NF-κB) levels in HUVECs and placentas were evaluated via Western blot and qRT-PCR.
  
  
  
  We demonstrated that miR-34a was highly enriched in goat placenta after cardiopulmonary bypass. Moreover, RCAN1 was identified as a novel direct target of miR-34a. Transfection of miR-34a led to decreased RCAN1 expression and increased NFATC1 and NF-κB expression in HUVECs. Conversely, inhibition of miR-34a rescued RCAN1 expression and reduced NFATC1 and NF-κB expression in HUVECs.
  
  
  
  We demonstrated a remarkable role of miR-34a as a regulator of NFATC1-associated placental inflammation through direct targeting of RCAN1. MiR-34a could serve as a novel therapeutic target for limiting the progression of placental inflammation after fetal cardiac bypass.
authors.affiliation: Department of Cardiovascular Surgery, Guangdong Cardiovascular Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China; Department of Maternal Fetal Medicine and Fetal Cardiology, Guangdong Cardiovascular Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China; Guangdong Provincial Key Laboratory of South China Structural Heart Disease, Guangzhou, China.
authors.forename: Hai-Yun
authors.initials: HY
authors.lastname: Yuan
authors.affiliation: Department of Cardiovascular Surgery, Guangdong Cardiovascular Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China; Department of Maternal Fetal Medicine and Fetal Cardiology, Guangdong Cardiovascular Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China; Guangdong Provincial Key Laboratory of South China Structural Heart Disease, Guangzhou, China.
authors.forename: Cheng-Bin
authors.initials: CB
authors.lastname: Zhou
authors.affiliation: Department of Cardiovascular Surgery, Guangdong Cardiovascular Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China; Guangdong Provincial Key Laboratory of South China Structural Heart Disease, Guangzhou, China.
authors.forename: Ji-Mei
authors.initials: JM
authors.lastname: Chen
authors.affiliation: Department of Cardiovascular Surgery, Guangdong Cardiovascular Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
authors.forename: Xiao-Bing
authors.initials: XB
authors.lastname: Liu
authors.affiliation: Department of Cardiovascular Surgery, Guangdong Cardiovascular Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China; Guangdong Provincial Key Laboratory of South China Structural Heart Disease, Guangzhou, China.
authors.forename: Shu-Sheng
authors.initials: SS
authors.lastname: Wen
authors.affiliation: Department of Cardiovascular Surgery, Guangdong Cardiovascular Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Xu
authors.affiliation: Department of Cardiovascular Surgery, Guangdong Cardiovascular Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China; Guangdong Provincial Key Laboratory of South China Structural Heart Disease, Guangzhou, China. Electronic address: drzhuangjian5413@163.com.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhuang
mesh_terms: D000818:Animals; D002315:Cardiopulmonary Bypass; D004730:Endothelium, Vascular / Q000378:metabolism*; D005260:Female; D006041:Goats; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D050778:NFATC Transcription Factors / Q000235:genetics / Q000378:metabolism; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D035683:MicroRNAs; D009124:Muscle Proteins; D016328:NF-kappa B; D050778:NFATC Transcription Factors
keywords: Cardiopulmonary bypass; Endothelial cells; Fetus; Inflammation; MicroRNAs; Placental insufficiency