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高血压的基因治疗。

Gene therapy for hypertension.

作者信息

Paulis Ludovit, Franke Heinrich, Simko Fedor

机构信息

a Institute of Pathophysiology, Faculty of Medicine , Comenius University , Bratislava , Slovakia.

b Institute of Normal and Pathological Physiology , Slovak Academy of Sciences , Bratislava , Slovakia.

出版信息

Expert Opin Biol Ther. 2017 Nov;17(11):1345-1361. doi: 10.1080/14712598.2017.1364726. Epub 2017 Aug 17.

Abstract

The control of hypertension and the resulting cardiovascular events is still insufficient. Thus, the search for novel means for blood pressure (BP) reduction remains worth further clinical and research attention. The advances in vector and construct design sketch the use of gene therapy in hypertension. Areas covered: We have searched for studies using gene therapy in hypertension reporting BP outcomes. We have identified 63 experimental studies demonstrating feasible targeting of the classical and new renin-angiotensin-aldosterone system, β1-adrenergic receptor, NO-cGMP axis, endothelin, natriuretic peptides, kallikrein system, cytochrome P-450 hydroxylase, oncogenes, growth factors, interleukins, angiopoietin-1, adrenomedullin or Klotho in small rodents. Expert opinion: The usual BP reduction was by 10-30 mmHg for up to several months. Some studies reported target organ damage attenuation or even survival prolongation. However, the concept did not reach the clinical phase, in contrast to other cardiovascular conditions. Increased gene transfection efficacy necessary for a systemic treatment, personalized identification of the implied aetiology from the multifactorial background and evidence from larger mammals are required for gene therapy to compete with the broad spectrum of current therapeutic options in hypertension. Until then, in the field of hypertension, gene modulation will provide a valuable research tool.

摘要

高血压的控制以及由此引发的心血管事件仍未得到充分解决。因此,寻找降低血压(BP)的新方法仍值得临床和研究进一步关注。载体和构建体设计的进展勾勒出基因疗法在高血压治疗中的应用前景。涵盖领域:我们检索了使用基因疗法治疗高血压并报告血压结果的研究。我们确定了63项实验研究,这些研究表明在小型啮齿动物中,经典和新型肾素-血管紧张素-醛固酮系统、β1-肾上腺素能受体、NO-cGMP轴、内皮素、利钠肽、激肽释放酶系统、细胞色素P-450羟化酶、癌基因、生长因子、白细胞介素、血管生成素-1、肾上腺髓质素或Klotho等靶点具有可行性。专家观点:通常血压可降低10 - 30 mmHg,持续数月。一些研究报告了靶器官损伤减轻甚至生存期延长。然而,与其他心血管疾病不同,该概念尚未进入临床阶段。基因疗法要与目前广泛的高血压治疗选择竞争,需要提高全身治疗所需的基因转染效率,从多因素背景中个性化识别潜在病因,以及来自大型哺乳动物的证据。在此之前,在高血压领域,基因调节将提供一个有价值的研究工具。

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