钙结合蛋白向成年心肌细胞的基因转移。
Gene Transfer of Calcium-Binding Proteins into Adult Cardiac Myocytes.
作者信息
Thompson Brian R, Cohen Houda, Angulski Addeli Bez Batti, Metzger Joseph M
机构信息
Department of Integrative Biology and Physiology, University of Minnesota Medical School, Minneapolis, MN, USA.
出版信息
Methods Mol Biol. 2019;1929:187-205. doi: 10.1007/978-1-4939-9030-6_12.
Heart failure is the leading cause of combined morbidity and mortality in the USA with 50% of cases being diastolic heart failure. Diastolic heart failure results from poor myocardial relaxation and inadequate filling of the left ventricular chamber caused in part by calcium-handling dysregulation. In this chapter we describe methods to investigate new approaches of novel human Ca binding protein motifs to restore normal Ca handling function to diseased myocardium. Gene transfer of parvalbumin into adult cardiac myocytes has been studied as a potential therapeutic, specifically as a strategic Ca buffer to correct cardiac mechanical dysfunction in disease. This chapter provides protocols for studying wild-type parvalbumin isoforms and parvalbumins with strategically designed EF-hand motifs in adult cardiac myocytes via acute adenoviral gene transfer. These protocols have been used extensively to optimize parvalbumin function as a potential therapeutic for failing heart muscle.
心力衰竭是美国发病率和死亡率合并的首要原因，其中50%的病例为舒张性心力衰竭。舒张性心力衰竭是由于心肌舒张功能不良以及左心室腔充盈不足所致，部分原因是钙处理失调。在本章中，我们描述了研究新型人类钙结合蛋白基序新方法的途径，以恢复患病心肌的正常钙处理功能。将小白蛋白基因转移到成年心肌细胞中已作为一种潜在治疗方法进行了研究，特别是作为一种战略性钙缓冲剂来纠正疾病中的心脏机械功能障碍。本章提供了通过急性腺病毒基因转移在成年心肌细胞中研究野生型小白蛋白亚型和具有经战略设计的EF手基序的小白蛋白的方案。这些方案已被广泛用于优化小白蛋白作为衰竭心肌潜在治疗方法的功能。
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