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Gene therapy for ischemic heart disease.

机译:缺血性心脏病的基因治疗。

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INTRODUCTION: Coronary artery disease (CAD) is still the leading cause of death in industrialized nations. Even though revascularization strategies such as percutaneous coronary intervention (PCI) and coronary artery bypass graft surgery (CABG) as well as drug therapy have significantly reduced mortality, about 30% of patients will develop chronic heart failure over time. Ischemic heart disease and heart failure are characterized by an adverse remodeling of the heart, featuring cardiomyocyte hypertrophy, increased fibrosis and capillary rarification. AREAS COVERED: Beside an assessment of current vector systems, this review focuses on potential target genes affecting angiogenesis/arteriogenesis and contractility. The potential of micro RNA (miRNA) modulation for the de-repression of survival and pro-angiogenic genes is discussed. Since gene therapy of the target region is preferable to avoid systemic contamination, application routes are discussed. Expert opinion: miRNAs are a promising new development for successful gene therapy, especially for acute myocardial infarction since their miRNA antagonists are easy to apply and appear to be selectively absorbed by the ischemic myocardial tissue. Rapid uptake and prolonged presence of known antimirs and antagomirs support this notion. For ischemic heart disease the most promising gene therapeutic approach seems to be the regional intravenous application of suitable AAV vectors and vascular growth factors, providing the full scope of angiogenesis, vessel maturation and collateral growth optionally combined with genes enhancing contractility.
机译:简介:在工业化国家,冠状动脉疾病(CAD)仍然是主要的死亡原因。尽管诸如经皮冠状动脉介入治疗(PCI)和冠状动脉旁路移植术(CABG)以及药物治疗等血运重建策略已显着降低了死亡率,但随着时间的流逝,约30%的患者会发展为慢性心力衰竭。缺血性心脏病和心力衰竭的特征是心脏的不良重塑,表现为心肌细胞肥大,纤维化增加和毛细血管稀疏。涵盖的领域:除了对当前载体系统的评估之外,本综述着重于影响血管生成/动脉生成和收缩力的潜在靶基因。讨论了微RNA(miRNA)调节对存活和促血管生成基因的抑制作用的潜力。由于优选靶区域的基因治疗以避免全身污染,因此讨论了应用途径。专家意见:miRNA是成功的基因疗法的有希望的新发展,特别是对于急性心肌梗塞,因为它们的miRNA拮抗剂易于使用,并且似乎被缺血性心肌组织选择性吸收。快速吸收和长期存在的已知的反病毒和抑癌药支持这一观点。对于缺血性心脏病,最有前途的基因治疗方法似乎是适当的AAV载体和血管生长因子的区域静脉应用,可提供血管生成,血管成熟和侧支生长的完整范围,并可选地结合增强收缩力的基因。

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