title: Catestatin increases the expression of anti-apoptotic and pro-angiogenetic factors in the post-ischemic hypertrophied heart of SHR.
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).
  
  
  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.
authors.affiliation: Department of Clinical and Biological Sciences, University of Turin, Torino, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Penna
authors.affiliation: Department of Biology, Ecology and Earth Sciences, University of Calabria, Arcavacata di Rende, Italy.
authors.forename: Teresa
authors.initials: T
authors.lastname: Pasqua
authors.affiliation: Department of Biology, Ecology and Earth Sciences, University of Calabria, Arcavacata di Rende, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Amelio
authors.affiliation: Department of Clinical and Biological Sciences, University of Turin, Torino, Italy.
authors.forename: Maria-Giulia
authors.initials: MG
authors.lastname: Perrelli
authors.affiliation: Department of Clinical and Biological Sciences, University of Turin, Torino, Italy.
authors.forename: Carmelina
authors.initials: C
authors.lastname: Angotti
authors.affiliation: Department of Clinical and Biological Sciences, University of Turin, Torino, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Tullio
authors.affiliation: VA San Diego Healthcare System, University of California, San Diego, California, United States of America.
authors.forename: Sushil K
authors.initials: SK
authors.lastname: Mahata
authors.affiliation: Department of Biology, Ecology and Earth Sciences, University of Calabria, Arcavacata di Rende, Italy; National Institute of Cardiovascular Research, Bologna, Italy.
authors.forename: Bruno
authors.initials: B
authors.lastname: Tota
authors.affiliation: Department of Clinical and Biological Sciences, University of Turin, Torino, Italy; National Institute of Cardiovascular Research, Bologna, Italy.
authors.forename: Pasquale
authors.initials: P
authors.lastname: Pagliaro
authors.affiliation: Department of Biology, Ecology and Earth Sciences, University of Calabria, Arcavacata di Rende, Italy; National Institute of Cardiovascular Research, Bologna, Italy.
authors.forename: Maria C
authors.initials: MC
authors.lastname: Cerra
authors.affiliation: Department of Biology, Ecology and Earth Sciences, University of Calabria, Arcavacata di Rende, Italy; National Institute of Cardiovascular Research, Bologna, Italy.
authors.forename: Tommaso
authors.initials: T
authors.lastname: Angelone
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis*; D006332:Cardiomegaly / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D053379:Chromogranin A / Q000494:pharmacology*; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D008297:Male; D017202:Myocardial Ischemia / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR
chemical_list: D051017:Apoptosis Regulatory Proteins; D053379:Chromogranin A; D010446:Peptide Fragments; C109084:chromogranin A (344-364)
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