title: Eccentric cardiac hypertrophy was induced by long-term intermittent hypoxia in rats.
abstract: It is unclear whether cardiac hypertrophy and hypertrophy-related pathways will be induced by long-term intermittent hypoxia. Thirty-six Sprague-Dawley rats were randomly assigned into three groups: normoxia, and long-term intermittent hypoxia (12% O(2), 8 h per day) for 4 weeks (4WLTIH) or for 8 weeks (8WLTIH). Myocardial morphology, trophic factors and signalling pathways in the three groups were determined by heart weight index, histological analysis, Western blotting and reverse transcriptase-polymerase chain reaction from the excised left ventricle. The ratio of whole heart weight to body weight, the ratio of left ventricular weight to body weight, the gross vertical cross-section of the heart and myocardial morphological changes were increased in the 4WLTIH group and were further augmented in the 8WLTIH group. In the 4WLTIH group, tumour necrosis factor-alpha(TNFalpha), insulin-like growth factor (IGF)-II, phosphorylated p38 mitogen-activated protein kinase (P38), signal transducers and activators of transcription (STAT)-1 and STAT-3 were significantly increased in the cardiac tissues. However, in the 8WLTIH group, in addition to the above factors, interleukin-6, mitogen-activated protein kinase (MEK)5 and extracellular signal-regulated kinase (ERK)5 were significantly increased compared with the normoxia group. We conclude that cardiac hypertrophy associated with TNFalpha and IGF-II was induced by intermittent hypoxia. The longer duration of intermittent hypoxia further activated the eccentric hypertrophy-related pathway, as well as the interleukin 6-related MEK5-ERK5 and STAT-3 pathways, which could result in the development of cardiac dilatation and pathology.
authors.affiliation: Center of General Education, Central Taiwan University of Science & Technology, Taichung, Taiwan.
authors.forename: Li-Mien
authors.initials: LM
authors.lastname: Chen
authors.forename: Wei-Wen
authors.initials: WW
authors.lastname: Kuo
authors.forename: Jaw-Ji
authors.initials: JJ
authors.lastname: Yang
authors.forename: Shyi-Gang P
authors.initials: SG
authors.lastname: Wang
authors.forename: Yu-Lan
authors.initials: YL
authors.lastname: Yeh
authors.forename: Fuu-Jen
authors.initials: FJ
authors.lastname: Tsai
authors.forename: Ying-Jui
authors.initials: YJ
authors.lastname: Ho
authors.forename: Mu-Hsin
authors.initials: MH
authors.lastname: Chang
authors.forename: Chih-Yang
authors.initials: CY
authors.lastname: Huang
authors.forename: Shin-Da
authors.initials: SD
authors.lastname: Lee
mesh_terms: D000818:Animals; D015153:Blotting, Western; D006332:Cardiomegaly / Q000209:etiology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D015870:Gene Expression; D000860:Hypoxia / Q000150:complications* / Q000378:metabolism; D007335:Insulin-Like Growth Factor II / Q000096:biosynthesis; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis* / Q000235:genetics; D015850:Interleukin-6 / Q000096:biosynthesis; D048671:MAP Kinase Kinase 5 / Q000096:biosynthesis; D020935:MAP Kinase Signaling System; D008297:Male; D048054:Mitogen-Activated Protein Kinase 7 / Q000096:biosynthesis; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D009929:Organ Size; D010766:Phosphorylation; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050794:STAT1 Transcription Factor / Q000096:biosynthesis; D050796:STAT3 Transcription Factor / Q000096:biosynthesis; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D048051:p38 Mitogen-Activated Protein Kinases / Q000096:biosynthesis
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D015850:Interleukin-6; D012333:RNA, Messenger; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; C494081:Stat1 protein, rat; C494088:Stat3 protein, rat; D014409:Tumor Necrosis Factor-alpha; D007335:Insulin-Like Growth Factor II; D048054:Mitogen-Activated Protein Kinase 7; D048051:p38 Mitogen-Activated Protein Kinases; D048671:MAP Kinase Kinase 5; C482565:Map2k5 protein, rat