Personalizing cardiac regenerative therapy: At the heart of Pim1 kinase

详细信息    查看全文

• 作者：Kaitlen Samse¹ ; Nirmala Hariharan² ; Mark A. Sussman ; ^{heartman4ever@icloud.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：MI ; myocardial infarction ; CPC ; cardiac progenitor cell ; NFκB ; nuclear factor kappa-light-chain-enhancer of activated B cells ; STAT ; signal transducers and activators of transcription ; PI3K ; phosphatidylinositide 3-kinases ; Klf5 ; kruppel-like factor 5 ; EGF ; epidermal growth factor ; LIF ; leukemia inhibitory factor ; Pim1-KO ; Pim1 knock-out ; TAC ; trans-aortic constriction ; hCPC ; human cardiac progenitor cell ; TERT ; telomerase reverse transcriptase ; CDK ; cyclin-dependent kinase ; NuMA ; nuclear mitoti
• 刊名：Pharmacological Research
• 出版年：2016
• 出版时间：January 2016
• 年：2016
• 卷：103
• 期：Complete
• 页码：13-16
• 全文大小：1033 K

文摘

During cardiac aging, DNA damage and environmental stressors contribute to telomeric shortening and human cardiac progenitor cells acquire a senescent phenotype that leads to decreased stem cell function. Reversion of this phenotype through genetic modification is essential to advance regenerative therapy. Studies in the cardiac specific overexpression and subcellular targeting of Pim1 kinase demonstrate its influence on regeneration, proliferation, survival, metabolism and senescence. The cardioprotective effects of Pim1 modification can be picked apart and enhanced by targeting the kinase to distinct subcellular compartments, allowing for selection of specific phenotypic traits after molecular modification. In this perspective, we examine the therapeutic implications of Pim1 to encourage the personalization of cardiac regenerative therapy.