Excellence Cluster Cardio-Pulmonary Institute (CPI), Universities of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Justus Liebig University of Giessen, Aulweg 130, 35392 Giessen, Germany.
Max Planck Institute for Heart and Lung Research, 61231 Bad Nauheim, Germany.
Int J Mol Sci. 2021 Jan 25;22(3):1179. doi: 10.3390/ijms22031179.
Pulmonary hypertension (PH) is a progressive complex fatal disease of multiple etiologies. Hyperproliferation and resistance to apoptosis of vascular cells of intimal, medial, and adventitial layers of pulmonary vessels trigger excessive pulmonary vascular remodeling and vasoconstriction in the course of pulmonary arterial hypertension (PAH), a subgroup of PH. Multiple gene mutation/s or dysregulated gene expression contribute to the pathogenesis of PAH by endorsing the proliferation and promoting the resistance to apoptosis of pulmonary vascular cells. Given the vital role of these cells in PAH progression, the development of safe and efficient-gene therapeutic approaches that lead to restoration or down-regulation of gene expression, generally involved in the etiology of the disease is the need of the hour. Currently, none of the FDA-approved drugs provides a cure against PH, hence innovative tools may offer a novel treatment paradigm for this progressive and lethal disorder by silencing pathological genes, expressing therapeutic proteins, or through gene-editing applications. Here, we review the effectiveness and limitations of the presently available gene therapy approaches for PH. We provide a brief survey of commonly existing and currently applicable gene transfer methods for pulmonary vascular cells in vitro and describe some more recent developments for gene delivery existing in the field of PH in vivo.
肺动脉高压（PH）是一种多病因的进行性复杂致命疾病。在肺动脉高压（PAH），即 PH 的一个亚组中，肺血管内膜、中膜和外膜的血管细胞过度增殖和抗凋亡触发了过度的肺血管重塑和血管收缩。多种基因突变/或基因表达失调通过促进肺血管细胞的增殖和抗凋亡，促进了 PAH 的发病机制。鉴于这些细胞在 PAH 进展中的重要作用，开发安全有效的基因治疗方法，导致基因表达的恢复或下调，通常涉及疾病的病因，是当务之急。目前，FDA 批准的药物都没有治愈 PH 的方法，因此创新的工具可能通过沉默病理性基因、表达治疗性蛋白，或通过基因编辑应用，为这种进行性和致命性疾病提供一种新的治疗模式。在这里，我们回顾了目前可用于 PH 的基因治疗方法的有效性和局限性。我们简要介绍了目前用于体外肺血管细胞的常用和现有的基因转移方法，并描述了 PH 领域中体内基因传递的一些最新进展。
