title: Compromised mitochondrial remodeling in compensatory hypertrophied myocardium of spontaneously hypertensive rat.
abstract: BACKGROUND
  Hypertension leads to cardiac hypertrophy as an adaptive response to increased workload. While initial development of hypertrophy is compensatory when contractile function is maintained, persistent stress on heart leads to deteriorated cardiac function and onset of heart failure. Mitochondrial dysfunction develops in the failing heart; however, whether it presents in compensatory cardiac hypertrophy is controversial.
  
  
  METHODS
  Spontaneously hypertensive rats (SHRs) and age-matched normotensive Wistar Kyoto rats were used in the study. Mitochondrial function and remodeling-related mechanisms in the left ventricles were measured by enzyme activity tests, Western blots, and reverse transcriptase polymerase chain reaction.
  
  
  RESULTS
  Compensatory cardiac hypertrophy in SHR was indicated by higher heart/weigh ratio, left ventricular systolic pressure and ±dp/dt(max) (P<.001, P<.05, and P<.01, respectively). Enzyme activities of mitochondrial complex I and II were significantly reduced (P<.05 and P<.01) in SHR in concert with decreased expression of complex subunits (P<.01 for NDUFS3, P=.068 for SDHB, and P<.05 for ATP5A1). Mitochondrial fission protein Drp1 was decreased (P<.05), while fusion protein OPA1 was increased (P<.01). Parkin and SirT1/AMPK-PGC-1α signaling, responsible for mitochondrial elimination and biogenesis respectively, were decreased in SHR (P<.01 for Parkin, P<.001 for SirT1 and p-AMPK).
  
  
  CONCLUSIONS
  Our results implicated that mitochondrial function and remodeling, indicated by mitochondrial enzyme activities and remodeling-related molecules, were compromised in compensatory hypertrophied myocardium of the SHR hypertensive model.
  
  
  CONCLUSIONS
  Mitochondrial function in compensatory hypertrophied myocardium is controversial. Our present study found mitochondrial dysfunction in the left ventricle of spontaneously hypertensive rats, which was possibly a result of compromised mitochondrial remodeling including mitochondrial dynamics, elimination, and biogenesis.
authors.affiliation: Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Life Science, FIST, Xi'an Jiaotong University, Xi'an 710049, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Tang
authors.affiliation: School of Life Science and Technology, Shaanxi Normal University, Xi'an 710026, China; Sports Ministry, Xi'an University of Science and Technology, Xi'an 710054, China.
authors.forename: Chunjuan
authors.initials: C
authors.lastname: Mi
authors.affiliation: Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Life Science, FIST, Xi'an Jiaotong University, Xi'an 710049, China.
authors.forename: Jiankang
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Physiology, Fourth Military Medical University, Xi'an 710032, China. Electronic address: fgao@fmmu.edu.cn.
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
authors.affiliation: Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Life Science, FIST, Xi'an Jiaotong University, Xi'an 710049, China. Electronic address: jglong@mail.xjtu.edu.cn.
authors.forename: Jiangang
authors.initials: J
authors.lastname: Long
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000818:Animals; D004195:Disease Models, Animal; D034281:Dynamins / Q000378:metabolism; D042967:Electron Transport Complex I / Q000378:metabolism; D020558:GTP Phosphohydrolases / Q000378:metabolism; D006973:Hypertension / Q000150:complications* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D017379:Hypertrophy, Left Ventricular / Q000209:etiology* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008929:Mitochondria, Heart / Q000378:metabolism / Q000473:pathology*; D025261:Mitochondrial Proton-Translocating ATPases / Q000378:metabolism; D063269:Mitochondrial Turnover; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D009245:NADH Dehydrogenase / Q000378:metabolism; D010086:Oxidative Phosphorylation Coupling Factors / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010766:Phosphorylation; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D015398:Signal Transduction; D056564:Sirtuin 1 / Q000378:metabolism; D013385:Succinate Dehydrogenase / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D016277:Ventricular Function, Left; D017725:Ventricular Pressure; D020257:Ventricular Remodeling
chemical_list: D010086:Oxidative Phosphorylation Coupling Factors; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; D014157:Transcription Factors; D013385:Succinate Dehydrogenase; D009245:NADH Dehydrogenase; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein; D055372:AMP-Activated Protein Kinases; C488368:Sirt1 protein, rat; D056564:Sirtuin 1; C000628217:F(6) ATPase; D020558:GTP Phosphohydrolases; C498811:Opa1 protein, rat; D025261:Mitochondrial Proton-Translocating ATPases; C519851:Dnm1l protein, rat; D034281:Dynamins; D042967:Electron Transport Complex I; C472512:NDUFS3 protein, human
keywords: Cardiac hypertrophy; Hypertension; Mitochondria; Spontaneously hypertensive rat