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

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• 作者：Anthony J.A. Molina ; PhD^a ; Manish S. Bharadwaj ; PhD^a ; Cynthia Van Horn ; PhD^a ; Barbara J. Nicklas ; PhD^a ; Mary F. Lyles ; MD^a ; Joel Eggebeen ; MS^b ; Mark J. Haykowsky ; PhD^c ; Peter H. Brubaker ; PhD^d ; Dalane W. Kitzman ; MD^b ; ^{dkitzman@wakehealth.edu" class="auth_mail" title="E-mail the corresponding author}
• 关键词：aging ; exercise ; heart failure ; mitochondria ; preserved ejection fraction ; skeletal muscle
• 刊名：JACC: Heart Failure
• 出版年：2016
• 出版时间：August 2016
• 年：2016
• 卷：4
• 期：8
• 页码：636-645
• 全文大小：731 K

文摘

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.