Nishihama Natsumi, Nagayama Takahiro, Makino Shinji, Koishi Ryuta
Venture Science Laboratories, R&D Division, Daiichi Sankyo Co., Ltd., 1-2-58, Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan.
Rare Disease Laboratories, R&D Division, Daiichi Sankyo Co., Ltd., 1-2-58, Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan.
Heliyon. 2019 Mar 13;5(3):e01292. doi: 10.1016/j.heliyon.2019.e01292. eCollection 2019 Mar.
Fat storage-inducing transmembrane proteins 1 and 2 (FITM1 and FITM2, respectively) are transmembrane endoplasmic/sarcoplasmic reticulum proteins involved in lipid droplet formation. The physiological functions of FITM1 have only been reported in skeletal muscle, while those of FITM2 were analyzed using genetically engineered mice. However, their roles in the heart have not been characterized. To examine their cardiac functions, we analyzed or -knockout mice. Neither constitutive (-/-) aged nor heart failure model mice showed significant differences in heart size or function. (-/-) mice exhibited embryonic death, and aged (+/-) mice had shortened left ventricular end-diastolic dimension, and shortened left ventricular end-systolic dimension. However, body weight and ejection fraction of (+/-) mice were similar to those of wild-type littermates. In the chronic heart failure models, (+/-) mice showed significant suppression of increased left ventricular end-diastolic dimension and reduced ejection fraction. These results suggest the involvement of in chronic heart failure, whereas have a minor effect in this context in mice.
脂肪储存诱导跨膜蛋白1和2（分别为FITM1和FITM2）是参与脂滴形成的跨膜内质网/肌浆网蛋白。FITM1的生理功能仅在骨骼肌中有报道，而FITM2的生理功能则通过基因工程小鼠进行分析。然而，它们在心脏中的作用尚未得到明确。为了研究它们在心脏中的功能，我们分析了FITM1或FITM2基因敲除小鼠。无论是组成型FITM1（-/-）老年小鼠还是心力衰竭模型小鼠，心脏大小或功能均无显著差异。FITM1（-/-）小鼠表现出胚胎死亡，而老年FITM1（+/-）小鼠的左心室舒张末期内径缩短，左心室收缩末期内径缩短。然而，FITM1（+/-）小鼠的体重和射血分数与野生型同窝小鼠相似。在慢性心力衰竭模型中，FITM1（+/-）小鼠的左心室舒张末期内径增加和射血分数降低得到显著抑制。这些结果表明FITM1参与慢性心力衰竭，而在这种情况下FITM2在小鼠中的作用较小。
