がん悪液質による心筋変化

今日は、がん悪液質による心筋変化をみた動物実験の論文を紹介します。

Min Tian, et al: Cardiac alterations in cancer-induced cachexia in mice. International Journal of Oncology 37(2):347-353, 2010

悪液質は広義のサルコペニアの要因の1つになり、骨格筋の減少が著明となります。しかし、がん悪液質が心不全の原因になるかどうかは明らかになっていません。

この動物実験の結果は、がん悪液質のマウスは心機能が低下し、その原因として線維化や心筋の変化だったそうです。仮説としては悪液質は骨格筋だけでなく、心筋も減少させて心機能を悪化させると言えます。

ただ、これも仮説ですが、悪液質に限らずすべてのサルコペニアで骨格筋だけでなく心筋も減少する可能性があります。病態的にはありうる話かと思いますが、十分な検証が今後必要です。

私が経験したのは、神経性食思不振症の方が肺炎などで重度侵襲となった結果、骨格筋だけでなく心筋も減少（心臓超音波で心筋が明らかに薄くなっていることで確認）して心不全となっていました。心不全の原因は心筋減少だけではないと思いますが。

サルコペニアをみたら心筋減少症・心機能障害を疑えという時代が来るかもしれません。まずは悪液質をみたら心筋減少症・心機能障害の可能性を考えましょう。

Abstract:
Cachexia is a common syndrome in advanced cancer patients and causes up to 22% of cancer-related deaths. It remains elusive whether cancer cachexia causes heart failure. We investigated the effect of cancer cachexia on heart function and cardiac muscle structure in a mouse model. Male CD2F1 mice were inoculated with either colon-26 adenocarcinoma cells (Tumor group) or vehicle (PBS) (No Tumor group and Pair-fed group). Heart function as measured by fractional shortening in vivo using transthoracic echocardiography was performed on day 14 after tumor or PBS inoculation. At necropsy (day 17), hearts were collected for histology, transmission electron microscopy, RT-PCR and SDS-PAGE analysis. Mice from the Tumor group displayed a significantly reduced fractional shortening compared to mice in the No Tumor and Pair-fed groups. In hearts of the Tumor mice compared to the other groups, there was marked fibrosis and transmission electron microscopy revealed disrupted myocardial ultrastructure. Gene expression of troponin I, a regulator of cardiac muscle contraction, was reduced. Moreover, both mRNA and protein levels of myosin heavy chain (MHC) were altered whereby MHCα (adult isoform) was decreased and MHCβ (fetal isoform) was increased indicating reactivation of the fetal gene expression pattern. In conclusion, heart function was diminished in mice with tumor-induced cachexia, and this impaired function was associated with increased fibrosis, disrupted myocardial structure and altered composition of contractile proteins of cardiac muscle.