Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, NE, USA.
Adv Exp Med Biol. 2023;1396:103-114. doi: 10.1007/978-981-19-5642-3_7.
Differential gene expression is associated with diabetic cardiomyopathy (DMCM) and culminates in adverse remodeling in the diabetic heart. Genome editing is a technology utilized to alter endogenous genes. Genome editing also provides an option to induce cardioprotective genes or inhibit genes linked to adverse cardiac remodeling and thus has promise in ameliorating DMCM. Non-coding genes have emerged as novel regulators of cellular signaling and may serve as potential therapeutic targets for DMCM. Specifically, there is a widespread change in the gene expression of fetal cardiac genes and microRNAs, termed genetic reprogramming, that promotes pathological remodeling and contributes to heart failure in diabetes. This genetic reprogramming of both coding and non-coding genes varies with the progression and severity of DMCM. Thus, genetic editing provides a promising option to investigate the role of specific genes/non-coding RNAs in DMCM initiation and progression as well as developing therapeutics to mitigate cardiac remodeling and ameliorate DMCM. This chapter will summarize the research progress in genome editing and DMCM and provide future directions for utilizing genome editing as an approach to prevent and/or treat DMCM.
差异基因表达与糖尿病心肌病（DMCM）相关，并最终导致糖尿病心脏的不良重构。基因组编辑是一种用于改变内源性基因的技术。基因组编辑还提供了诱导心脏保护基因或抑制与不良心脏重构相关基因的选择，因此在改善 DMCM 方面具有潜力。非编码基因已成为细胞信号转导的新型调节剂，可能成为 DMCM 的潜在治疗靶点。具体而言，存在胎儿心脏基因和 microRNAs 的基因表达的广泛变化，称为基因重编程，其促进病理性重构并导致糖尿病中的心力衰竭。这种编码和非编码基因的遗传重编程随 DMCM 的进展和严重程度而变化。因此，基因编辑为研究特定基因/非编码 RNA 在 DMCM 起始和进展中的作用以及开发减轻心脏重构和改善 DMCM 的治疗方法提供了有前途的选择。本章将总结基因组编辑和 DMCM 的研究进展，并为利用基因组编辑作为预防和/或治疗 DMCM 的方法提供未来方向。
