Development of therapies for severe ischemic cardiomyopathy to substute heart transplantation

唯一有效的治疗缺血性心肌病的方法是心脏移植。然而，在日本，只有数量有限的捐助者。因此，我们试图建立一种新的替代心脏移植策略。对心脏搭桥手术中获得的人动脉内膜切除术样本和心外膜脂肪的组织学分析显示，炎症细胞如巨噬细胞和T细胞浸润增强，不仅在血管壁，而且在血管周围脂肪组织。我们还发现脂肪细胞释放的无细胞DNA与巨噬细胞上的TLR9之间的相互作用在脂肪组织的慢性炎症中起着至关重要的作用。基于这些观察结果，我们开始开发一种新的手术策略，通过外源性动脉和皮下脂肪组织重建冠状动脉来治疗缺血性心肌病患者。

The only effective therapy for ischemic cardiomyopathy is heart transplantation. However, only limited numbers of donors are available in Japan. Therefore, we tried to establish a new strategy to substitute heart transplantation. Histological analysis of human endarterectomy samples and epicardial fat obtained during cardiac bypass surgery revealed enhanced infiltration of inflammatory cells such as macrophages and T cells not only in vessel wall but also in perivascular adipose tissues. We also found that interaction between cell-free DNA released from adipocytes and TLR9 on macrophages plays a crucial role in chronic inflammation in adipose tissues. Based on these observations, we started to develop a new surgical strategy to treat patients with ischemic cardiomyopathy by reconstructing coronary artery with exogenous artery and subcutaneous adipose tissues.