Gao Ling, Cui Weina, Zhang Pengyuan, Jang Albert, Zhu Wuqiang, Zhang Jianyi
Department of Biomedical Engineering, School of Medicine and School of Engineering, University of Alabama at Birmingham, Birmingham, Alabama, 35233, United States of America.
Department of Medicine, Cardiology Division, University of Minnesota-Twin Cities, Minneapolis, Minnesota, 55455, United States of America.
PLoS One. 2016 Sep 8;11(9):e0162149. doi: 10.1371/journal.pone.0162149. eCollection 2016.
Utilizing a fast 31P magnetic resonance spectroscopy (MRS) 2-dimensional chemical shift imaging (2D-CSI) method, this study examined the heterogeneity of creatine kinase (CK) forward flux rate of hearts with postinfarction left ventricular (LV) remodeling. Immunosuppressed Yorkshire pigs were assigned to 4 groups: 1) A sham-operated normal group (SHAM, n = 6); 2) A 60 minutes distal left anterior descending coronary artery ligation and reperfusion (MI, n = 6); 3) Open patch group; ligation injury plus open fibrin patch over the site of injury (Patch, n = 6); and 4) Cell group, hiPSCs-cardiomyocytes, -endothelial cells, and -smooth muscle cells (2 million, each) were injected into the injured myocardium pass through a fibrin patch (Cell+Patch, n = 5). At 4 weeks, the creatine phosphate (PCr)/ATP ratio, CK forward flux rate (Flux PCr→ATP), and k constant of CK forward flux rate (kPCr→ATP) were severely decreased at border zone myocardium (BZ) adjacent to MI. Cell treatment results in significantly increase of PCr/ATP ratio and improve the value of kPCr→ATP and Flux PCr→ATP in BZ myocardium. Moreover, the BZ myocardial CK total activity and protein expression of CK mitochondria isozyme and CK myocardial isozyme were significantly reduced, but recovered in response to cell treatment. Thus, cell therapy results in improvement of BZ bioenergetic abnormality in hearts with postinfarction LV remodeling, which is accompanied by significantly improvements in BZ CK activity and CK isozyme expression. The fast 2D 31P MR CSI mapping can reliably measure the heterogeneity of bioenergetics in hearts with post infarction LV remodeling.
本研究采用快速31P磁共振波谱（MRS）二维化学位移成像（2D-CSI）方法，检测了心肌梗死后左心室（LV）重构心脏中肌酸激酶（CK）正向通量率的异质性。将免疫抑制的约克夏猪分为4组：1）假手术正常组（SHAM，n = 6）；2）左前降支冠状动脉远端结扎60分钟并再灌注组（MI，n = 6）；3）开放补片组，结扎损伤加在损伤部位覆盖开放纤维蛋白补片（补片，n = 6）；4）细胞组，将人诱导多能干细胞来源的心肌细胞、内皮细胞和平滑肌细胞（各200万）通过纤维蛋白补片注入受损心肌（细胞+补片，n = 5）。4周时，与心肌梗死相邻的边缘区心肌（BZ）的磷酸肌酸（PCr）/三磷酸腺苷（ATP）比值、CK正向通量率（Flux PCr→ATP）和CK正向通量率的k常数（kPCr→ATP）显著降低。细胞治疗使BZ心肌的PCr/ATP比值显著升高，并改善了kPCr→ATP和Flux PCr→ATP的值。此外，BZ心肌CK总活性以及CK线粒体同工酶和CK心肌同工酶的蛋白表达显著降低，但经细胞治疗后恢复。因此，细胞治疗可改善心肌梗死后LV重构心脏BZ的生物能量异常，同时BZ的CK活性和CK同工酶表达也显著改善。快速二维31P MR CSI图谱能够可靠地测量心肌梗死后LV重构心脏生物能量学的异质性。
