嵌合腺相关病毒介导的缺血性心脏病心血管重编程
Chimeric Adeno-Associated Virus-Mediated Cardiovascular Reprogramming for Ischemic Heart Disease.
作者信息
Yoo So Young, Jeong Su-Nam, Kang Jeong-In, Lee Seung-Wuk
机构信息
BIO-IT Foundry Technology Institute, Pusan National University, Busan 46241, Republic of Korea.
Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan 50612, Republic of Korea.
出版信息
ACS Omega. 2018 May 31;3(5):5918-5925. doi: 10.1021/acsomega.8b00904.
Here, we demonstrated chimeric adeno-associated virus (chimeric AAV), AAV-DJ-mediated cardiovascular reprogramming strategy to generate new cardiomyocytes and limit collagen deposition in cardiac fibroblasts by inducing synergism of chimeric AAV-expressing Gata4, Mef2c, Tbx5 (AAV-GMT)-mediated heart reprogramming and chimeric AAV-expressing thymosin β4 (AAV-Tβ4)-mediated heart regeneration. AAV-GMT promoted a gradual increase in expression of cardiac-specific genes, including Actc1, Gja1, Myh6, Ryr2, and cTnT, with a gradual decrease in expression of a fibrosis-specific gene, procollagen type I and here AAV-Tβ4 help to induce GMT expression, providing a chimeric AAV-mediated therapeutic cell reprogramming strategy for ischemic heart diseases.
在此，我们展示了嵌合腺相关病毒（chimeric AAV），即AAV-DJ介导的心血管重编程策略，通过诱导表达嵌合AAV的Gata4、Mef2c、Tbx5（AAV-GMT）介导的心脏重编程与表达嵌合AAV的胸腺素β4（AAV-Tβ4）介导的心脏再生之间的协同作用，来生成新的心肌细胞并限制心脏成纤维细胞中的胶原蛋白沉积。AAV-GMT促进了心脏特异性基因（包括Actc1、Gja1、Myh6、Ryr2和cTnT）表达的逐渐增加，同时纤维化特异性基因I型前胶原的表达逐渐降低，并且在此AAV-Tβ4有助于诱导GMT表达，为缺血性心脏病提供了一种嵌合AAV介导的治疗性细胞重编程策略。
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