Improvement in cardiac function with small intestine extracellular matrix is associated with recruitment of C-kit cells, myofibroblasts, and macrophages after myocardial infarction
Authors: Ning-Ping Wang
John D Puskas
Robert Matheny
Zhi-Qing Zhao
Robert A Guyton
Mario Mosunjac
Jakob Vinten-Johansen
Di Xu
Journal: Journal of the American College of Cardiology (2010)
Discipline: CLINICAL MEDICINE
Keywords: angiogenesis; cardiac function; small intestine extracellular matrix emulsion (EMU); c-kit cells; myofibroblasts
Affiliations: Cardiovascular Research Laboratory, Mercer University School of Medicine, Savannah, Georgia. Electronic address: ., Cardiothoracic Research Laboratory, Department of Pathology, Carlyle Fraser Heart Center/Crawford Long Hospital, Emory University, Atlanta, Georgia., Cardiovascular Research Laboratory, Mercer University School of Medicine, Savannah, Georgia., CorMatrix Cardiovascular, Inc., Atlanta, Georgia.

Abstract:  Objectives: This study tested the hypothesis that modulation of angiogenesis and cardiac function by injecting small intestine extracellular matrix emulsion (EMU) into myocardium is associated with recruitment of c-kit cells, myofibroblasts, and macrophages after myocardial infarction. Background: Degradation of native extracellular matrix has been associated with adverse cardiac remodeling after infarction. Methods: Sixty-four rats were subjected to 45 min ischemia followed by 3, 7, 21, and 42 days of reperfusion, respectively. Saline or EMU (30 to 50 microl) was injected into the area at risk myocardium after reperfusion. Histological examination was performed by immunohistochemical staining, and cardiac function was analyzed using echocardiography. Results: The population of c-kit-positive cells in infarcted myocardium with the EMU injection increased significantly relative to the saline control at 7 days of reperfusion. Along with this change, alpha-smooth muscle actin expressing myofibroblasts and macrophages accumulated to a significant extent compared with the saline control. Increased vascular endothelial growth factor protein level and strong immunoreactivity of vascular endothelial growth factor expression were observed. Angiogenesis in the EMU area was significantly enhanced relative to the saline control, evidenced by increased density of alpha-smooth muscle actin positive vessels. Furthermore, echocardiography showed significant improvements in fractional shortening, ejection fraction, and stroke volume in the EMU group. The wall thickness of the infarcted middle anterior septum in the EMU group was significantly increased relative to the saline control. Conclusions: We show for the first time that injection of EMU into the infarcted myocardium increases neovascularization and preserves cardiac function, potentially mediated by enhanced recruitment of c-kit-positive cells, myofibroblasts, and macrophages. 

Retracted: No

PubPeer comments:
 Figure 7. Some features appear to be visible multiple times within the same panel, or between panels. Boxes of the same color and shape highlight some (but not all) areas that look similar. ![file] , 
 Figure 6 appears to show some repetitive features in at least one of the panels. There might be more. ![file] , 
 Working backwards, the top part of Figure 5 appears to show two panels with an overlapping area, except for some parts with red staining. ![file] , 
 Unfortunate errors appeared to show two panels with an overlapping area in Figure 5, one panel with repetitive features in Figure 6, and some visible features within the same panel in Figure 7. Since the original data were not available to retrieve the source of these figures, we decided to retract this article. We regret the effect of this action on the work of other investigators for any inconvenience caused, and apologize to the editors of Journal of the American College and Cardiology. , 
 Dear Dr. Zhao, thank you for your quick reply. The issues in Figure 5 do not appear to be a simple overlap, but rather an overlap with some features removed or added. My drawing of the blue puzzle pieces highlight areas that look similar between the two panels, but the indentations in the puzzle pieces focus attention to red stained areas that are present or absent in one of the panels. I thank you for your decision to retract the paper. , 
 Dear Dr. Zhao, It s eight months later, without any visible action at the paper s landing page. Could you please give us an update on the retraction of this paper? , 
 #6 Rather than a retraction, the authors actually issued a correction on June 30 this year, see here: https: doi.org 10.1016 j.jacc.2020.05.046 The correction says:  In the above paper, Figures 5, 6, and 7 have been removed as unfortunate errors appeared to show two panelswith some features removed or added in Figure 5, one panel with repetitive features in Figure 6, and multiplepanels with visible identical area within the same panel in Figure 7. Since this study was conducted in 2007 and original data is not available, the authors cannot retrieve the source of these figures. The authors apologize for these errors. The online version of the article has been corrected to reflect these changes. IMO, removing 3 figures does not make it a retraction or even a correction. Very interesting decision from the journal. , 
 It is interesting that the authors decided to retract the paper, but that the journal apparently decided a correction was enough. I featured the decision to issue a correction - instead of a retraction - for this paper in my blog post  JACC wins the first u201cThis Image Is Fineu201d Award - https: scienceintegritydigest.com 2020 04 13 jacc-wins-the-first-this-image-is-fine-award , 
 The main concern with these partially-duplicated images is that the authors do not seem to be aware how they came to exist. So while it is true that the statistical analyses do not rest directly on these figures, so that removal of the figures does not affect the results, the possibility remains that the quantified data that **do** affect the results are equally problematical. , 
 The other commenters may wish to analyze Figure 3 as well. There may be some portions of bands that appear more than once. *** Closeup of inverse image ![file] *** Original ![file] , 
 #10 Po-S staining was performed on the second day using the same film after the expression of stem cell factor was identified by Western blot assay. Although the bands of Po-S staining seem to be identical, but, it was not exactly same. There was no way to change or modify these bands, but it was also unnecessary. As you can see above these two bands, the expression of stem cell factor was different. , 
 #9 Thank you for your supportive comments. Removal of these figures did not affect the quantitative statistical analysis because the mean in every group was obtained from 8 animals. These figures only provided a representative samples showing group difference. But, we apologize for the errors made in this article. ,