Catestatin increases the expression of anti-apoptotic and pro-angiogenetic factors in the post-ischemic hypertrophied heart of SHR.

Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE

Original Publication: San Francisco, CA : Public Library of Science

Apoptosis Regulatory Proteins/*biosynthesis ; Cardiomegaly/*metabolism ; Chromogranin A/*pharmacology ; Gene Expression Regulation/*drug effects ; Myocardial Ischemia/*metabolism ; Myocardium/*metabolism ; Peptide Fragments/*pharmacology; Animals ; Cardiomegaly/drug therapy ; Cardiomegaly/pathology ; Disease Models, Animal ; Female ; Male ; Myocardial Ischemia/drug therapy ; Myocardial Ischemia/pathology ; Myocardium/pathology ; Rats ; Rats, Inbred SHR

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.

Retraction in: PLoS One. 2021 Feb 4;16(2):e0246900. (PMID: 33539473)

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0 (Apoptosis Regulatory Proteins)
0 (Chromogranin A)
0 (Peptide Fragments)
0 (chromogranin A (344-364))

Date Created: 20140808 Date Completed: 20150411 Latest Revision: 20220321

20231215

PMC4123866

10.1371/journal.pone.0102536

25099124