title: MicroRNA profiling of the intestine during hypothermic circulatory arrest in swine.
abstract: OBJECTIVE
  To perform a profiling analysis of changes in intestinal microRNA (miRNA) expression during hypothermic circulatory arrest (HCA).
  
  
  METHODS
  A total of eight piglets were randomly divided into HCA and sham operation (SO) groups. Under general anesthesia, swine in the HCA group were subjected to hypothermic cardiopulmonary bypass at 24 °C followed by 80 min of circulatory arrest, and the reperfusion lasted for 180 min after cross-clamp removal. The counterparts in the SO group were only subjected to median sternotomy. Histopathological analysis was used to detect mucosal injury, and Pick-and-Mix custom miRNA real-time polymerase chain reaction (PCR) panels containing 306 unique primer sets were utilized to assay unpooled intestinal samples harvested from the two groups.
  
  
  RESULTS
  The intestinal mucosa of the animals that were subjected to 24 °C HCA exhibited representative ischemic reperfusion injury of grade 2 or 3 according to the Chiu score. Such intestinal mucosal injuries, with the subepithelial space and epithelial layer lifting away from the lamina propria, were accompanied by shortened and irregular villi. On the contrary, the intestinal mucosa remained normal in the sham-operated animals. In total, twenty-five miRNAs were differentially expressed between the two groups (15 upregulated and 10 downregulated in the HCA group). Among these, eight miRNAs (miR-122, miR-221-5p, miR-31, miR-421-5p, miR-4333, miR-499-3p, miR-542 and let-7d-3p) were significantly dysregulated (four higher and four lower). The expression of miR-122 was significantly (5.37-fold) increased in the HCA group vs the SO group, indicating that it may play a key role in HCA-induced mucosal injury.
  
  
  CONCLUSIONS
  Exposure to HCA caused intestinal miRNA dysregulation and barrier dysfunction in swine. These altered miRNAs might be related to the protection or destruction of the intestinal barrier.
authors.affiliation: Wei-Bin Lin, Meng-Ya Liang, Guang-Xian Chen, Xiao Yang, Han Qin, Jian-Ping Yao, Kang-Ni Feng, Zhong-Kai Wu, 2 Department of Cardiac Surgery, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, Guangdong Province, China.
authors.forename: Wei-Bin
authors.initials: WB
authors.lastname: Lin
authors.affiliation: Wei-Bin Lin, Meng-Ya Liang, Guang-Xian Chen, Xiao Yang, Han Qin, Jian-Ping Yao, Kang-Ni Feng, Zhong-Kai Wu, 2 Department of Cardiac Surgery, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, Guangdong Province, China.
authors.forename: Meng-Ya
authors.initials: MY
authors.lastname: Liang
authors.affiliation: Wei-Bin Lin, Meng-Ya Liang, Guang-Xian Chen, Xiao Yang, Han Qin, Jian-Ping Yao, Kang-Ni Feng, Zhong-Kai Wu, 2 Department of Cardiac Surgery, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, Guangdong Province, China.
authors.forename: Guang-Xian
authors.initials: GX
authors.lastname: Chen
authors.affiliation: Wei-Bin Lin, Meng-Ya Liang, Guang-Xian Chen, Xiao Yang, Han Qin, Jian-Ping Yao, Kang-Ni Feng, Zhong-Kai Wu, 2 Department of Cardiac Surgery, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, Guangdong Province, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Yang
authors.affiliation: Wei-Bin Lin, Meng-Ya Liang, Guang-Xian Chen, Xiao Yang, Han Qin, Jian-Ping Yao, Kang-Ni Feng, Zhong-Kai Wu, 2 Department of Cardiac Surgery, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, Guangdong Province, China.
authors.forename: Han
authors.initials: H
authors.lastname: Qin
authors.affiliation: Wei-Bin Lin, Meng-Ya Liang, Guang-Xian Chen, Xiao Yang, Han Qin, Jian-Ping Yao, Kang-Ni Feng, Zhong-Kai Wu, 2 Department of Cardiac Surgery, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, Guangdong Province, China.
authors.forename: Jian-Ping
authors.initials: JP
authors.lastname: Yao
authors.affiliation: Wei-Bin Lin, Meng-Ya Liang, Guang-Xian Chen, Xiao Yang, Han Qin, Jian-Ping Yao, Kang-Ni Feng, Zhong-Kai Wu, 2 Department of Cardiac Surgery, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, Guangdong Province, China.
authors.forename: Kang-Ni
authors.initials: KN
authors.lastname: Feng
authors.affiliation: Wei-Bin Lin, Meng-Ya Liang, Guang-Xian Chen, Xiao Yang, Han Qin, Jian-Ping Yao, Kang-Ni Feng, Zhong-Kai Wu, 2 Department of Cardiac Surgery, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, Guangdong Province, China.
authors.forename: Zhong-Kai
authors.initials: ZK
authors.lastname: Wu
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D020869:Gene Expression Profiling / Q000379:methods; D005819:Genetic Markers; D006324:Heart Arrest, Induced / Q000009:adverse effects*; D007036:Hypothermia, Induced / Q000009:adverse effects*; D007413:Intestinal Mucosa / Q000098:blood supply* / Q000378:metabolism* / Q000473:pathology; D065666:Mesenteric Ischemia / Q000209:etiology / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D035683:MicroRNAs / Q000378:metabolism*; D010539:Permeability; D060888:Real-Time Polymerase Chain Reaction; D015427:Reperfusion Injury / Q000209:etiology / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D013552:Swine
chemical_list: D005819:Genetic Markers; D035683:MicroRNAs
keywords: Animal model; Barrier function; Cardiopulmonary bypass; MicroRNA; Randomized controlled trial; Reperfusion injury