Catestatin increases the expression of anti-apoptotic and pro-angiogenetic factors in the post-ischemic hypertrophied heart of SHR
Authors: Teresa Pasqua
Francesca Tullio
Tommaso Angelone
Daniela Amelio
Claudia Penna
Carmelina Angotti
Bruno Tota
Sushil K Mahata
Maria-Giulia Perrelli
Pasquale Pagliaro
Maria C Cerra
Journal: PLoS ONE (2014)
Discipline: Multidisciplinary
Keywords: comorbidities; cardioprotective strategies; Chromogranin A-derived peptide; Catestatin; RISK-pathway activation
Affiliations: Department of Clinical and Biological Sciences, University of Turin, Torino, Italy., Department of Biology, Ecology and Earth Sciences, University of Calabria, Arcavacata di Rende, Italy., VA San Diego Healthcare System, University of California, San Diego, California, United States of America., Department of Biology, Ecology and Earth Sciences, University of Calabria, Arcavacata di Rende, Italy; National Institute of Cardiovascular Research, Bologna, Italy., Department of Clinical and Biological Sciences, University of Turin, Torino, Italy; National Institute of Cardiovascular Research, Bologna, Italy.

Abstract:  Background: In the presence of comorbidities the effectiveness of many cardioprotective strategies is blunted. The goal of this study was to assess in a hypertensive rat model if the early reperfusion with anti-hypertensive and pro-angiogenic Chromogranin A-derived peptide, Catestatin (CST:hCgA352-372; CST-Post), protects the heart via Reperfusion-Injury-Salvage-Kinases (RISK)-pathway activation, limiting infarct-size and apoptosis, and promoting angiogenetic factors (e.g., hypoxia inducible factor, HIF-1α, and endothelial nitric oxide synthase, eNOS, expression). Methods and results: The effects of CST-Post on infarct-size, apoptosis and pro-angiogenetic factors were studied in isolated hearts of spontaneously hypertensive rats (SHR), which underwent the following protocols: (a) 30-min ischemia and 120-min reperfusion (I/R); (b) 30-min ischemia and 20-min reperfusion (I/R-short), both with and without CST-Post (75 nM for 20-min at the beginning of reperfusion). In unprotected Wistar-Kyoto hearts, used as normal counterpart, infarct-size resulted smaller than in SHR. CST-Post reduced significantly infarct-size and improved post-ischemic cardiac function in both strains. After 20-min reperfusion, CST-Post induced S-nitrosylation of calcium channels and phosphorylation of RISK-pathway in WKY and SHR hearts. Yet specific inhibitors of the RISK pathway blocked the CST-Post protective effects against infarct in the 120-min reperfusion groups. Moreover, apoptosis (evaluated by TUNEL, ARC and cleaved caspase) was reduced by CST-Post. Importantly, CST-Post increased expression of pro-angiogenetic factors (i.e., HIF-1α and eNOS expression) after two-hour reperfusion. Conclusions: CST-Post limits reperfusion damages and reverses the hypertension-induced increase of I/R susceptibility. Moreover, CST-Post triggers antiapoptotic and pro-angiogenetic factors suggesting that CST-Post can be used as an anti-maladaptive remodeling treatment. 

Retracted: Yes

PubPeer comments:
null, 
 Retracted, February 4, 2021. The notice reads:  Following the publication of this article [1], concerns were raised regarding the results presented in Figure 6. Specifically, the following results appear similar: * Lane 2 of the p-ERK1 2 panel, Lane 1 of the ERK1 2 panel, lane 2 of the ERK1 2 panel, and lane 3 of the ERK1 2 panel when flipped. * Lane 1 and 2 of the p-PKCu03b5 panel and lane 1 and 2 of the PKCu03b5 panel when flipped. The u03b2-Actin panels for the PKCu03b5 and GSK-3u03b2 samples * Lane 3 of the p-PKCu03b5 and Lanes 3 of the u03b2-Actin panels (PKCu03b5 and GSK-3u03b2) when flipped. * Lane 1 and lane 3 of the GSK-3u03b2 panel. The corresponding author commented that the wrong image was inadvertently included in the published article as Figure 6. The authors offered to replace Figure 6 with a corrected version and provided replicate image data to support the Figure 6 results. They also noted that the experimental and control data for Figure 6 were obtained on parallel blots. However, the information and data provided did not clarify the above concerns, and as such concerns remain about the integrity and reliability of the published figure. In light of the unresolved concerns about Figure 6, the PLOS ONE Editors retract this article. CP, TP, DA, MGP, CA, SKM, BT, PP, MCC, and TA agreed with the retraction, stand by the articleu2019s findings, and apologise for the issues with the published article. FT either did not respond directly or could not be reached. In addition, during the assessment of these concerns it came to light that there was a potential competing interest between the handling Academic Editor and one or more authors. We regret that this was not identified and addressed prior to the articleu2019s publication. I was Peer 1, and I reported these concerns to the journal in August 2014. I thank the authors and PLOS ONE staff for their time and effort in addressing these concerns. ,