Lai Zhong-Fang
Department of Pharmacology and Molecular Therapeutics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
Recent Pat Cardiovasc Drug Discov. 2009 Nov;4(3):203-10. doi: 10.2174/157489009789152285.
Recently, regenerative medicine using the transplantation of embryonic stem cells and bone marrow stem cells has been a great success but still has many unconfirmed problems including its clinical evaluation. The aim of this article is to review current literature and some patents regarding molecular therapeutic agents including using MAP kinase TNNI3K for the treatment and diagnosis of acute myocardial ischemia or infarction. TNNI3K is a novel cardiac troponin I-interacting kinase gene and its overexpression may promote cardiac myogenesis, improve cardiac performance, and attenuate ischemia-induced ventricular remodeling. The modulation of embryonal stem cells with high TNNI3K activity using a TNNI3K active peptide could be a useful therapeutic approach for ischemic cardiac diseases. For overexpressing TNNI3K or enhancing TNNI3K activity in cardiac precursor cells, the engraftment of bone marrow cells or embryonic stem cells can effectively promote cardiac myogenesis, beating frequency, and contractile functions, and decrease "silent" (no contraction) cardiac cells after cell transplantion, indicating that the overexpression of TNNI3K can increase the success rate of transplanting embryonic stem cells or bone marrow cells into ischemic hearts for the treatment of ischemic cardiac diseases. Although previous investigations showing that TNNI3K may be involved in the development of cardiac hypertrophy, it is still unclear whether TNNI3K has a role in cardiac hypertrophy or what mechanism is involved in the effects of TNNI3K. To confirm this, further investigations need to be undertaken.
最近，使用胚胎干细胞和骨髓干细胞移植的再生医学取得了巨大成功，但仍存在许多未确认的问题，包括其临床评估。本文的目的是综述当前关于分子治疗剂的文献和一些专利，包括使用丝裂原活化蛋白激酶TNNI3K治疗和诊断急性心肌缺血或梗死。TNNI3K是一种新型的与心肌肌钙蛋白I相互作用的激酶基因，其过表达可能促进心肌生成，改善心脏功能，并减轻缺血诱导的心室重塑。使用TNNI3K活性肽调节具有高TNNI3K活性的胚胎干细胞可能是治疗缺血性心脏病的一种有用的治疗方法。为了在心脏前体细胞中过表达TNNI3K或增强TNNI3K活性，骨髓细胞或胚胎干细胞的植入可以有效地促进心肌生成、搏动频率和收缩功能，并减少细胞移植后“沉默”（无收缩）的心肌细胞，这表明TNNI3K的过表达可以提高将胚胎干细胞或骨髓细胞移植到缺血心脏中治疗缺血性心脏病的成功率。尽管先前的研究表明TNNI3K可能参与心肌肥大的发展，但仍不清楚TNNI3K在心肌肥大中是否起作用或TNNI3K的作用涉及何种机制。为了证实这一点，需要进行进一步的研究。
