Idi1 and Hmgcs2 Are Affected by Stretch in HL-1 Atrial Myocytes

Chih-Yuan Fang, Mien-Cheng Chen, Tzu-Hao Chang, Chia-Chen Wu, Jen-Ping Chang, Hsien-Da Huang, Wan-Chun Ho, Yi-Zhen Wang, Kuo-Li Pan, Yu-Sheng Lin, Yao-Kuang Huang, Chien-Jen Chen, Wei-Chieh Lee

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Background: Lipid expression is increased in the atrial myocytes of mitral regurgitation (MR) patients. This study aimed to investigate key regulatory genes and mechanisms of atrial lipotoxic myopathy in MR. Methods: The HL-1 atrial myocytes were subjected to uniaxial cyclic stretching for eight hours. Fatty acid metabolism, lipoprotein signaling, and cholesterol metabolism were analyzed by PCR assay (168 genes). Results: The stretched myocytes had significantly larger cell size and higher lipid expression than non-stretched myocytes (all p < 0.001). Fatty acid metabolism, lipoprotein signaling, and cholesterol metabolism in the myocytes were analyzed by PCR assay (168 genes). In comparison with their counterparts in non-stretched myocytes, seven genes in stretched monocytes (Idi1, Olr1, Nr1h4, Fabp2, Prkag3, Slc27a5, Fabp6) revealed differential upregulation with an altered fold change >1.5. Nine genes in stretched monocytes (Apoa4, Hmgcs2, Apol8, Srebf1, Acsm4, Fabp1, Acox2, Acsl6, Gk) revealed differential downregulation with an altered fold change <0.67. Canonical pathway analysis, using Ingenuity Pathway Analysis software, revealed that the only genes in the superpathway of cholesterol biosynthesis were Idi1 (upregulated) and Hmgcs2 (downregulated). The fraction of stretched myocytes expressing Nile red was significantly decreased by RNA interference of Idi1 (p < 0.05) and was significantly decreased by plasmid transfection of Hmgcs2 (p = 0.004). Conclusions: The Idi1 and Hmgcs2 genes have regulatory roles in atrial lipotoxic myopathy associated with atrial enlargement.
Original languageEnglish
Article number4094
JournalInternational Journal Of Molecular Sciences
Volume19
Issue number12
DOIs
StatePublished - Dec 2018

Keywords

  • atrium; genes; lipid; myopathy

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