中文摘要
申请人围绕心力衰竭(心衰)中心肌细胞兴奋收缩耦联调控机制开展研究,在阐明心衰的心脏结构与功能变化关系及关键调控机制方面取得系列成绩,1.证明心肌细胞兴奋收缩耦联效率下降(时程延长)是心衰的特征表型,设计了用于早期心衰检测的兴奋收缩耦联时间诊断仪,获国家发明专利授权;2.发现心肌细胞横管与肌质网耦联结构受损是心肌细胞兴奋-收缩耦联效率下降的重要原因;3.发现导致心肌细胞兴奋收缩耦联结构紊乱和功能衰退的关键分子(JP2)并发现其调控分子(miR-24);基于miR-24上游特殊二级结构G-四链体,发现一种抑制心衰中miR-24异常升高的天然小分子。上述部分发现已被国际文献和临床检测结果证实,近5年,申请人发表SCI论文29篇,他引555次,其中以通讯或第一作者(含共同)在《Circulation Research》等期刊发表论文13篇。拟进一步开展基于核酸二级结构的心衰网络表观遗传调控研究。
英文摘要
The applicant conducted investigations on the regulation mechanisms of excitation-contraction coupling in cardiomyocytes of heart failure (HF), and achieved breakthroughs in elucidating the relationships between cardiac structural and functional alterations in failing hearts and the key underlying regulatory mechanisms. The major scientific achievements of the applicant include: 1. Proved that the decrease of excitation-contraction coupling efficiency (prolonged duration) is a characteristic feature of heart failure, and designed a diagnostic instrument for early detection of heart failure according to the excitation-contraction coupling duration, and it has been granted national invention patents; 2. Identified that the impairment of coupling structure between transverse tubules (TTs) and sarcoplasmic reticulum (SR) is an important factor leading to the decrease of cardiac excitation-contraction coupling efficiency during heart failure; 3. Discovered the key molecule (JP2) in the progression of excitation-contraction coupling disorder and cardiac dysfunction, and the regulatory molecule (miR-24) for JP2 expression, and further proposed a natural small molecule suppressing the abnormal elevation of miR-24 in failing hearts, based on G-quadruplex, a specific secondary structure of nucleic acids at the upstream of miR-24. Some of these findings have been confirmed by clinical examinations, and international peer research. These findings have paved new roads for the prevention and treatment of HF. The applicant has published 29 SCI articles during the past five years, with a total of 555 times cited by other SCI papers. Among these articles, 13 were published on journals, including Circulation Research, with the applicant as the corresponding or first (including co-first/corresponding author) author. The applicant will further investigate the epigenetic regulation network of heart failure based on the secondary structure of nucleic acids.
