Huq Fawzia, Del Monte Federica, Hajjar Roger J
Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02129, USA.
J Card Fail. 2002 Dec;8(6 Suppl):S389-400. doi: 10.1054/jcaf.2002.129249.
Gene transfer to the heart is a novel concept that holds great promise both as a therapeutic and an experimental tool. With the advent of improved vector technology and new insights into the pathophysiology of heart failure, it is now possible to target specific intracellular signaling pathways by adenoviral gene transfer. By over or under expressing a specific protein, complex pathways can be probed specifically, and the role of various molecular targets within crucial intracellular pathways can be more precisely defined. This review highlights recent advances made in the field of myocardial gene transfer, with an emphasis on how manipulation of signal transduction pathways by adenoviral gene transfer has been used to elucidate the pathophysiology underlying abnormal cardiac phenotypes that lead to cardiac failure, such as hypertrophy, contractile dysfunction, and apoptosis.
基因转移至心脏是一个全新的概念,作为一种治疗手段和实验工具都具有巨大的潜力。随着载体技术的改进以及对心力衰竭病理生理学有了新的认识,现在通过腺病毒基因转移能够靶向特定的细胞内信号通路。通过过表达或低表达特定蛋白质,可以特异性地探究复杂的信号通路,并且能够更精确地确定关键细胞内通路中各种分子靶点的作用。本综述重点介绍了心肌基因转移领域的最新进展,着重阐述了如何通过腺病毒基因转移来操纵信号转导通路,以此阐明导致心力衰竭的异常心脏表型(如肥大、收缩功能障碍和细胞凋亡)背后的病理生理学机制。