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首页> 外文期刊>Gene Therapy and Molecular Biology >Epigenetic and gene therapy in cardiovasculardiseases: an appraisal
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Epigenetic and gene therapy in cardiovasculardiseases: an appraisal

机译：表观遗传和基因疗法在心血管疾病中的评估

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Modifications of DNA and its nuclear environment (i.e. chromatin) may underlie cardiovascular diseases (CVD) and aging. Epigenetic alterations in chromatin (e.g. histone acetylation) have been directly implicated in the modulation of myocardial gene expression in progressive CVD, including cardiac hypertrophy. Cytosine methylation which can lead to gene inactivation has also been linked to increased levels of homocysteine, an important CVD disease risk factor. Advances in the identification of genes affected in CVD has lead to improved therapies either by the use of gene replacement and/or gene suppression (silencing) methodologies. Preclinical studies have shown that therapeutic gene transfer can provide beneficial results in treating heart failure, myocardial protection, hypertension, hypertrophy, cardiac arrhythmias and myocarditis as well as in disorders of the vascular wall where drug therapy has often proved to be of limited value. While early phases of clinical gene therapy trials for CVD have shown promising results in particular with therapeutic angiogenesis and restenosis treatment, the development of improved vectors, methods of delivery, and the acquisition of safety and toxicity data are critically needed before the use of these therapies can be indicated in a clinical setting. In this review, we will survey the current information available on the role of epigenetic modifications in CVD, and examine the present status and prospects for clinical use of epigenetic and gene therapy.
机译：DNA及其核环境（即染色质）的修饰可能是心血管疾病（CVD）和衰老的基础。染色质的表观遗传学改变（例如组蛋白乙酰化）直接参与了进行性CVD中心肌基因表达的调节，包括心肌肥大。可能导致基因失活的胞嘧啶甲基化也与同型半胱氨酸水平升高有关，同型半胱氨酸水平是重要的CVD疾病危险因素。通过使用基因替代和/或基因抑制（沉默）方法，鉴定受CVD影响的基因的进展已导致治疗方法的改善。临床前研究表明，治疗性基因转移可在治疗心力衰竭，心肌保护，高血压，肥大，心律不齐和心肌炎以及血管壁疾病（其中药物治疗通常被证明价值有限）方面提供有益的结果。尽管针对CVD的临床基因治疗试验的早期阶段已经显示出令人鼓舞的结果，尤其是在治疗性血管生成和再狭窄治疗方面，但在使用这些疗法之前，迫切需要开发改进的载体，递送方法以及获取安全性和毒性数据可以在临床环境中指示。在这篇综述中，我们将调查表观遗传修饰在CVD中的作用的现有信息，并探讨表观遗传和基因疗法在临床上的应用现状和前景。

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