Yaoita Hiroyuki, Maruyama Yukio
First Department of Internal Medicine, Fukushima Medical University, Hikarigaoka 1, Fukushima 960-1295, Japan.
Heart Fail Rev. 2008 Jun;13(2):181-91. doi: 10.1007/s10741-007-9074-6.
Apoptosis plays an important role in pathogenesis of primary and secondary cardiomyopathies. It is proposed that antiapoptotic interventions may constitute an effective strategy for these diseases. Some of the antiapoptotic interventions are "old wine in a new bottle" measures already included in the conventional pharmacotherapy. As specific antiapoptotic treatment, caspase inhibitors and anti-TNF-alpha antibody are in early phases of clinical trials in non-cardiac diseases or being contemplated for clinical studies. Non-pharmacotherapies such as cardiac resynchronization and left ventricular assist device also exert cardioprotection partly by antiapoptotic mechanisms. In the field of regenerative medicine, myocardial transplantation of bone marrow-derived stem cells has been performed. Although it is controversial whether it is a true regenerative medicine or the cytokine therapy, antiapoptotic effect of transplanted cells may also have a role in cardioprotection. Moreover, apoptosis may develop despite efforts for cardioprotection in some severe situations of heart failure. Cardiac repair and regeneration by cardiac stem cells may compensate a loss of cardiomyocytes avoiding a deleterious situation. Therefore, protection and/or potentiation of such effects by cardiac stem cells appear to be promising therapeutic strategy in the future. In this review, we discuss about the antiapoptotic interventions for cardiomyopathies in the "real world" and the future of clinical cardiology.
细胞凋亡在原发性和继发性心肌病的发病机制中起着重要作用。有人提出,抗凋亡干预可能是治疗这些疾病的有效策略。一些抗凋亡干预措施是传统药物治疗中已有的“换汤不换药”的方法。作为特异性抗凋亡治疗,半胱天冬酶抑制剂和抗TNF-α抗体在非心脏疾病的临床试验中处于早期阶段或正考虑用于临床研究。心脏再同步化治疗和左心室辅助装置等非药物治疗也部分通过抗凋亡机制发挥心脏保护作用。在再生医学领域,已开展了骨髓源性干细胞的心肌移植。尽管这是真正的再生医学还是细胞因子治疗存在争议,但移植细胞的抗凋亡作用可能也在心脏保护中发挥作用。此外,在某些严重心力衰竭情况下,尽管采取了心脏保护措施,细胞凋亡仍可能发生。心脏干细胞的心脏修复和再生可能弥补心肌细胞的损失,避免有害情况的发生。因此,保护和/或增强心脏干细胞的这种作用似乎是未来很有前景的治疗策略。在这篇综述中,我们讨论了心肌病在“现实世界”中的抗凋亡干预措施以及临床心脏病学的未来。