title: Differential Mitochondrial Function in Remodeled Right and Nonremodeled Left Ventricles in Pulmonary Hypertension.
abstract: OBJECTIVE
  Right ventricular failure is the primary reason for mortality in pulmonary hypertension (PH), but little is understood about the energetics of the failing right myocardium. Our aim was to examine mitochondrial function and proteomic signatures in paired remodeled right (RM-RV) and non-remodeled left (NRM-LV) ventricular tissue samples procured during heart-lung transplantation.
  
  
  RESULTS
  Contractile dysfunction in RM-RV and preserved contractile function in NRM-LV were determined clinically and by echocardiography. Mitochondria were isolated from fresh paired RV and LV wall specimens of explanted hearts. Respiratory states in response to 4 substrates and an uncoupler were analyzed. Proteomic analysis on the mitochondrial isolates was performed with the use of liquid chromatography-mass spectrometry. The RM-RV mitochondria exhibited higher succinate state 4 levels with lower respiratory control ratio (RCR) compared with state 4 levels for pyruvate-malate (PM) and glutamate-malate (GM). RM-RV mitochondria also exhibited lower state 3 for palmitoyl-carnitine (PC) and state 4 for all complex I substrates compared with NRM-LV. The mean RCR were greater in RM-RVs than in NRM-LVs for PM and GM, which is consistent with tight coupling (low state 4 rates, higher RCRs); however, low RM-RV state 3 rates suggest concurrent substrate-dependent impairment in respiratory capacity. Mitochondrial proteomics revealed greater levels of mitochondrial ADP-ATP translocase and proteins of ATP synthesis, mitochondrial pyruvate and short branched chain acyl-CoA metabolism in RM-RV.
  
  
  CONCLUSIONS
  The mitochondrial respiration and proteomics in RM-RV are different from NRM-LV. These results have important implications in expanding our understanding of RV metabolism and future management of RV failure.
authors.affiliation: Bioenergetics Program, Houston Methodist Research Institute, Weill Cornell Medical College, Houston, Texas.
authors.forename: Anisha A
authors.initials: AA
authors.lastname: Gupte
authors.affiliation: Methodist DeBakey Heart and Vascular Institute, Houston Methodist Research Institute, Houston, Texas.
authors.forename: Andrea M
authors.initials: AM
authors.lastname: Cordero-Reyes
authors.affiliation: Methodist DeBakey Heart and Vascular Institute, Houston Methodist Research Institute, Houston, Texas.
authors.forename: Keith A
authors.initials: KA
authors.lastname: Youker
authors.affiliation: Proteomics Programmatic Core Laboratory, Houston Methodist Research Institute, Houston, Texas.
authors.forename: Risë K
authors.initials: RK
authors.lastname: Matsunami
authors.affiliation: Proteomics Programmatic Core Laboratory, Houston Methodist Research Institute, Houston, Texas.
authors.forename: David A
authors.initials: DA
authors.lastname: Engler
authors.affiliation: Bioenergetics Program, Houston Methodist Research Institute, Weill Cornell Medical College, Houston, Texas.
authors.forename: Shumin
authors.initials: S
authors.lastname: Li
authors.affiliation: Methodist DeBakey Heart and Vascular Institute, Houston Methodist Research Institute, Houston, Texas; Department of Cardiovascular Surgery, Houston Methodist Research Institute, Weill Cornell Medical College, Houston, Texas.
authors.forename: Matthias
authors.initials: M
authors.lastname: Loebe
authors.affiliation: Methodist DeBakey Heart and Vascular Institute, Houston Methodist Research Institute, Houston, Texas; Department of Cardiology, Houston Methodist Research Institute, Weill Cornell Medical College, Houston, Texas.
authors.forename: Guha
authors.initials: G
authors.lastname: Ashrith
authors.affiliation: Methodist DeBakey Heart and Vascular Institute, Houston Methodist Research Institute, Houston, Texas; Department of Cardiology, Houston Methodist Research Institute, Weill Cornell Medical College, Houston, Texas; Catedra de Cardiologia y Medicina Vascular, Tecnologico de Monterrey, Nuevo Leon, Mexico.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Torre-Amione
authors.affiliation: Bioenergetics Program, Houston Methodist Research Institute, Weill Cornell Medical College, Houston, Texas; Department of Medicine, Houston Methodist Research Institute, Weill Cornell Medical College, Houston, Texas. Electronic address: djhamilton@houstonmethodist.org.
authors.forename: Dale J
authors.initials: DJ
authors.lastname: Hamilton
mesh_terms: D000293:Adolescent; D000368:Aged; D004452:Echocardiography; D042967:Electron Transport Complex I / Q000378:metabolism; D005260:Female; D006333:Heart Failure / Q000209:etiology / Q000503:physiopathology*; D006352:Heart Ventricles / Q000503:physiopathology*; D006801:Humans; D006976:Hypertension, Pulmonary / Q000150:complications*; D008875:Middle Aged; D008929:Mitochondria, Heart / Q000201:enzymology / Q000378:metabolism*; D000226:Mitochondrial ADP, ATP Translocases / Q000378:metabolism; D040901:Proteomics; D018497:Ventricular Dysfunction, Right / Q000209:etiology / Q000503:physiopathology*; D020257:Ventricular Remodeling
chemical_list: D000226:Mitochondrial ADP, ATP Translocases; D042967:Electron Transport Complex I
keywords: Mitochondria; pulmonary hypertension; remodeling; right ventricle