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Skeletal Muscle Mitochondrial Content, Oxidative Capacity, and Mfn2 Expression Are Reduced in Older Patients With Heart Failure and Preserved Ejection Fraction and Are Related to Exercise Intolerance.
Molina, Anthony J A; Bharadwaj, Manish S; Van Horn, Cynthia; Nicklas, Barbara J; Lyles, Mary F; Eggebeen, Joel; Haykowsky, Mark J; Brubaker, Peter H; Kitzman, Dalane W.
Afiliação
  • Molina AJ; Gerontology Section, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina.
  • Bharadwaj MS; Gerontology Section, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina.
  • Van Horn C; Gerontology Section, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina.
  • Nicklas BJ; Gerontology Section, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina.
  • Lyles MF; Gerontology Section, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina.
  • Eggebeen J; Cardiology Section, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina.
  • Haykowsky MJ; College of Nursing and Health Innovation, University of Texas at Arlington, Arlington, Texas.
  • Brubaker PH; Department of Exercise and Health Science, Wake Forest University, Winston-Salem, North Carolina.
  • Kitzman DW; Cardiology Section, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina. Electronic address: dkitzman@wakehealth.edu.
JACC Heart Fail ; 4(8): 636-45, 2016 08.
Article em En | MEDLINE | ID: mdl-27179829
ABSTRACT

OBJECTIVES:

The aim of this study was to examine skeletal muscle mitochondria content, oxidative capacity, and the expression of key mitochondrial dynamics proteins in patients with heart failure with preserved ejection fraction (HFpEF), as well as to determine potential relationships with measures of exercise performance.

BACKGROUND:

Multiple lines of evidence indicate that severely reduced peak exercise oxygen uptake (peak VO2) in older patients with HFpEF is related to abnormal skeletal muscle oxygen utilization. Mitochondria are key regulators of skeletal muscle metabolism; however, little is known about how these organelles are affected in HFpEF.

METHODS:

Both vastus lateralis skeletal muscle citrate synthase activity and the expression of porin and regulators of mitochondrial fusion were examined in older patients with HFpEF (n = 20) and healthy, age-matched control subjects (n = 17).

RESULTS:

Compared with age-matched healthy control subjects, mitochondrial content assessed by porin expression was 46% lower (p = 0.01), citrate synthase activity was 29% lower (p = 0.01), and Mfn2 (mitofusin 2) expression was 54% lower (p <0.001) in patients with HFpEF. Expression of porin was significantly positively correlated with both peak VO2 and 6-min walk distance (r = 0.48, p = 0.003 and r = 0.33, p = 0.05, respectively). Expression of Mfn2 was also significantly positively correlated with both peak VO2 and 6-min walk distance (r = 0.40, p = 0.02 and r = 0.37, p = 0.03 respectively).

CONCLUSIONS:

These findings suggest that skeletal muscle oxidative capacity, mitochondrial content, and mitochondrial fusion are abnormal in older patients with HFpEF and might contribute to their severe exercise intolerance.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Consumo de Oxigênio / Volume Sistólico / Tolerância ao Exercício / Proteínas Mitocondriais / Músculo Quadríceps / GTP Fosfo-Hidrolases / Insuficiência Cardíaca / Mitocôndrias Musculares Tipo de estudo: Observational_studies Limite: Aged / Female / Humans / Male / Middle aged Idioma: En Revista: JACC Heart Fail Ano de publicação: 2016 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Consumo de Oxigênio / Volume Sistólico / Tolerância ao Exercício / Proteínas Mitocondriais / Músculo Quadríceps / GTP Fosfo-Hidrolases / Insuficiência Cardíaca / Mitocôndrias Musculares Tipo de estudo: Observational_studies Limite: Aged / Female / Humans / Male / Middle aged Idioma: En Revista: JACC Heart Fail Ano de publicação: 2016 Tipo de documento: Article