運動療法は慢性心不全骨格筋のMuRF-1を減衰

運動療法は慢性心不全患者の骨格筋のMuRF-1発現を減衰させるという論文を紹介します。

Stephan Gielen, et al: Exercise Training Attenuates MuRF-1 Expression in the Skeletal Muscle of Patients with Chronic Heart Failure Independent of Age: The Randomized Leipzig Exercise Intervention in Chronic Heart Failure and Aging (LEICA) Catabolism Study. CIRCULATION Published online before print May 7, 2012, doi: 10.1161/CIRCULATIONAHA.111.047381

下記のHPで全文見ることができます。

http://circ.ahajournals.org/content/early/2012/05/07/CIRCULATIONAHA.111.047381.full.pdf

MuRF-1(Muscle RING-Finger Protein-1)は骨格筋、心筋に特異的に発現するE3型ユビキチンリガーゼであり、筋肉に関連する萎縮の責任分子と考えられています。今回の研究は運動でどの蛋白分解経路が変化するかを調査しています。

対象は慢性心不全患者と健常者60人ずつです。介入群は4週間の運動療法を行い、対照群は通常の臨床ケアを受けました。結果ですが、ベースラインのMuRF-1は慢性心不全患者で有意に高値でしたが、運動でMuRF-1の発現は有意に低下しました。

これより慢性心不全患者の筋萎縮（悪液質、広義のサルコペニア）にはMuRF-1の増加が関与していて、運動療法によってMuRF-1の発現が減衰されるという結論です。おそらくその結果、筋肉量、筋力の増強を期待できるのだと思います。

慢性心不全患者で筋萎縮（広義のサルコペニア）を認めた場合、その原因は加齢、活動、栄養（飢餓）、疾患（悪液質）の複数が合併していることが多いと思われます。何らかの検査マーカーでどの要素が大きいかがわかるようになると、リハ栄養をより行いやすくなるのになあと感じます。

Abstract

Background—Muscle wasting occurs both in chronic heart failure (CHF) and in normal aging and contributes to exercise intolerance and increased morbidity/mortality. However, the molecular mechanisms of muscle atrophy in CHF and their interaction with aging are still largely unknown. We therefore measured the activation of the ubiquitin-proteasome system (UPS) Min muscle biopsies of CHF patients and healthy controls (HC) in two age strata and assessed the age-dependent effects of a 4-week endurance training program on the catabolic-anabolic balance.

Methods and Results—60 CHF patients (30 patients≤55 years, mean age 46±5 years; 30 patients≥65 years, 72±5 years) and 60 healthy controls (HC, 30≤55 years, 50±5 years; 30≥65 years, 72±4 years) were randomized to 4 weeks of supervised endurance training or to a control group. Before and after the intervention vastus lateralis muscle biopsies were obtained. The expression of cathepsin-L, the muscle-specific E3 ligases MuRF-1 and MAFbx were measured by real-time PCR and confirmed by Western blot. At baseline MuRF-1 expression was significantly higher in CHF patients versus HC (mRNA: 624±59 versus 401±25 rel. units; p=0.007). After four weeks of exercise training MuRF-1 mRNA expression was reduced by -32.8% (p=0.02) in CHF patients ≤55 years and by -37.0% (p<0.05) in CHF patients ≥65 years.

Conclusions—MuRF-1, a component of the ubiquitin-proteasome system involved in muscle proteolysis, is increased in the skeletal muscle of patients with heart failure. Exercise training results in reduced MuRF-1 levels, suggesting that it blocks UPS activation, and does so in both younger and older CHF patients.