Abstract
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.
Highlights
Myocardial ATP demand per minute exceeds the amount of ATP present in myocardium of the heart by up to four orders of magnitude [1]; the ATP machinery must be able to continually resynthesize amount of ATP just as much as it can be utilized at contractile apparatusPLOS ONE | DOI:10.1371/journal.pone.0162149 September 8, 2016
Most of the human induced pluripotent stem cell (hiPSC)-CMs expressed cardiac troponin I (Fig 1A), cardiac troponin T (Fig 1B), and α sarcomeric actin (Fig 1C), and cardiac connexin 43 was present at numerous points of contact between adjacent cells; 20%-30% of the hiPSC-CMs expressed the 2v isoform of myosin light-chain (MLC-2v) (Fig 1B), which is present only in ventricular CMs. hiPSC-ECs and hiPSC-SMCs were generated via established differentiation protocols [13, 15] and expressed EC-specific (CD31, CD144, and von Willebrand factor 8 [vWF-8]) (Fig 1D–1F) or SMC-specific (α smooth-muscle actin [α-smooth muscle actin (αSMA)], smooth muscle 22α (SM22), and calponin) (Fig 1G–1I) proteins, respectively
Deficiencies in cellular ATP machinery and Creatine kinase (CK) forward ATP flux systems have long been thought to contribute to the progressive declines in myocardial function that occur in patients with left ventricular hypertrophy (LVH) [4, 33]
Summary
Myocardial ATP demand per minute exceeds the amount of ATP present in myocardium of the heart by up to four orders of magnitude [1]; the ATP machinery must be able to continually resynthesize amount of ATP just as much as it can be utilized at contractile apparatus
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
