Somatostatin and Its Receptors in Myocardial Ischemia/Reperfusion Injury and Cardioprotection
Little is known about the role of the neuropeptide somatostatin (SST) in myocardial ischemia/reperfusion injury and cardioprotection. Here, we investigated the direct cardiocytoprotective effect of SST on ischemia/reperfusion injury in cardiomyocyte cultures, as well as the expression of SST and its...
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Frontiers Media S.A.
2021
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oai:doaj.org-article:dcbc88f896f543ad8ae2da1ca762c8602021-11-05T08:36:32ZSomatostatin and Its Receptors in Myocardial Ischemia/Reperfusion Injury and Cardioprotection1663-981210.3389/fphar.2021.663655https://doaj.org/article/dcbc88f896f543ad8ae2da1ca762c8602021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fphar.2021.663655/fullhttps://doaj.org/toc/1663-9812Little is known about the role of the neuropeptide somatostatin (SST) in myocardial ischemia/reperfusion injury and cardioprotection. Here, we investigated the direct cardiocytoprotective effect of SST on ischemia/reperfusion injury in cardiomyocyte cultures, as well as the expression of SST and its receptors in pig and human heart tissues. SST induced a bell-shaped, concentration-dependent cardiocytoprotection in both adult rat primary cardiomyocytes and H9C2 cells subjected to simulated ischemia/reperfusion injury. Furthermore, in a translational porcine closed-chest acute myocardial infarction model, ischemic preconditioning increased plasma SST-like immunoreactivity. Interestingly, SST expression was detectable at the protein, but not at the mRNA level in the pig left ventricles. SSTR1 and SSTR2, but not the other SST receptors, were detectable at the mRNA level by PCR and sequencing in the pig left ventricle. Moreover, remote ischemic conditioning upregulated SSTR1 mRNA. Similarly, SST expression was also detectable in healthy human interventricular septum samples at the protein level. Furthermore, SST-like immunoreactivity decreased in interventricular septum samples of patients with ischemic cardiomyopathy. SSTR1, SSTR2, and SSTR5 but not SST and the other SST receptors were detectable at the mRNA level by sequencing in healthy human left ventricles. In addition, in healthy human left ventricle samples, SSTR1 and SSTR2 mRNAs were expressed especially in vascular endothelial and some other cell types as detected by RNA Scope®in situ hybridization. This is the first demonstration that SST exerts a direct cardiocytoprotective effect against simulated ischemia/reperfusion injury. Moreover, SST is expressed in the heart tissue at the peptide level; however, it is likely to be of sensory neural origin since its mRNA is not detectable. SSTR1 and SSTR2 might be involved in the cardioprotective action of SST, but other mechanisms cannot be excluded.Imre VörösImre VörösÉva SághyKrisztina PohóczkyKrisztina PohóczkyKrisztina PohóczkyAndrás MakkosAndrás MakkosZsófia OnódiZsófia OnódiGábor B. BrennerGábor B. BrennerTamás BaranyaiBence ÁggBence ÁggBence ÁggBarnabás VáradiÁgnes KeményÁgnes KeményÁgnes KeményPrzemyslaw LeszekAnikó GörbeAnikó GörbeZoltán V. VargaZoltán V. VargaZoltán GiriczZoltán GiriczRainer SchulzZsuzsanna HelyesZsuzsanna HelyesPéter FerdinandyPéter FerdinandyFrontiers Media S.A.articlesomatostatinsomatostatin receptorischemia-reperfusionmyocardial infarctionischemic conditioningtranslational researchTherapeutics. PharmacologyRM1-950ENFrontiers in Pharmacology, Vol 12 (2021) |
| institution |
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| collection |
DOAJ |
| language |
EN |
| topic |
somatostatin somatostatin receptor ischemia-reperfusion myocardial infarction ischemic conditioning translational research Therapeutics. Pharmacology RM1-950 |
| spellingShingle |
somatostatin somatostatin receptor ischemia-reperfusion myocardial infarction ischemic conditioning translational research Therapeutics. Pharmacology RM1-950 Imre Vörös Imre Vörös Éva Sághy Krisztina Pohóczky Krisztina Pohóczky Krisztina Pohóczky András Makkos András Makkos Zsófia Onódi Zsófia Onódi Gábor B. Brenner Gábor B. Brenner Tamás Baranyai Bence Ágg Bence Ágg Bence Ágg Barnabás Váradi Ágnes Kemény Ágnes Kemény Ágnes Kemény Przemyslaw Leszek Anikó Görbe Anikó Görbe Zoltán V. Varga Zoltán V. Varga Zoltán Giricz Zoltán Giricz Rainer Schulz Zsuzsanna Helyes Zsuzsanna Helyes Péter Ferdinandy Péter Ferdinandy Somatostatin and Its Receptors in Myocardial Ischemia/Reperfusion Injury and Cardioprotection |
| description |
Little is known about the role of the neuropeptide somatostatin (SST) in myocardial ischemia/reperfusion injury and cardioprotection. Here, we investigated the direct cardiocytoprotective effect of SST on ischemia/reperfusion injury in cardiomyocyte cultures, as well as the expression of SST and its receptors in pig and human heart tissues. SST induced a bell-shaped, concentration-dependent cardiocytoprotection in both adult rat primary cardiomyocytes and H9C2 cells subjected to simulated ischemia/reperfusion injury. Furthermore, in a translational porcine closed-chest acute myocardial infarction model, ischemic preconditioning increased plasma SST-like immunoreactivity. Interestingly, SST expression was detectable at the protein, but not at the mRNA level in the pig left ventricles. SSTR1 and SSTR2, but not the other SST receptors, were detectable at the mRNA level by PCR and sequencing in the pig left ventricle. Moreover, remote ischemic conditioning upregulated SSTR1 mRNA. Similarly, SST expression was also detectable in healthy human interventricular septum samples at the protein level. Furthermore, SST-like immunoreactivity decreased in interventricular septum samples of patients with ischemic cardiomyopathy. SSTR1, SSTR2, and SSTR5 but not SST and the other SST receptors were detectable at the mRNA level by sequencing in healthy human left ventricles. In addition, in healthy human left ventricle samples, SSTR1 and SSTR2 mRNAs were expressed especially in vascular endothelial and some other cell types as detected by RNA Scope®in situ hybridization. This is the first demonstration that SST exerts a direct cardiocytoprotective effect against simulated ischemia/reperfusion injury. Moreover, SST is expressed in the heart tissue at the peptide level; however, it is likely to be of sensory neural origin since its mRNA is not detectable. SSTR1 and SSTR2 might be involved in the cardioprotective action of SST, but other mechanisms cannot be excluded. |
| format |
article |
| author |
Imre Vörös Imre Vörös Éva Sághy Krisztina Pohóczky Krisztina Pohóczky Krisztina Pohóczky András Makkos András Makkos Zsófia Onódi Zsófia Onódi Gábor B. Brenner Gábor B. Brenner Tamás Baranyai Bence Ágg Bence Ágg Bence Ágg Barnabás Váradi Ágnes Kemény Ágnes Kemény Ágnes Kemény Przemyslaw Leszek Anikó Görbe Anikó Görbe Zoltán V. Varga Zoltán V. Varga Zoltán Giricz Zoltán Giricz Rainer Schulz Zsuzsanna Helyes Zsuzsanna Helyes Péter Ferdinandy Péter Ferdinandy |
| author_facet |
Imre Vörös Imre Vörös Éva Sághy Krisztina Pohóczky Krisztina Pohóczky Krisztina Pohóczky András Makkos András Makkos Zsófia Onódi Zsófia Onódi Gábor B. Brenner Gábor B. Brenner Tamás Baranyai Bence Ágg Bence Ágg Bence Ágg Barnabás Váradi Ágnes Kemény Ágnes Kemény Ágnes Kemény Przemyslaw Leszek Anikó Görbe Anikó Görbe Zoltán V. Varga Zoltán V. Varga Zoltán Giricz Zoltán Giricz Rainer Schulz Zsuzsanna Helyes Zsuzsanna Helyes Péter Ferdinandy Péter Ferdinandy |
| author_sort |
Imre Vörös |
| title |
Somatostatin and Its Receptors in Myocardial Ischemia/Reperfusion Injury and Cardioprotection |
| title_short |
Somatostatin and Its Receptors in Myocardial Ischemia/Reperfusion Injury and Cardioprotection |
| title_full |
Somatostatin and Its Receptors in Myocardial Ischemia/Reperfusion Injury and Cardioprotection |
| title_fullStr |
Somatostatin and Its Receptors in Myocardial Ischemia/Reperfusion Injury and Cardioprotection |
| title_full_unstemmed |
Somatostatin and Its Receptors in Myocardial Ischemia/Reperfusion Injury and Cardioprotection |
| title_sort |
somatostatin and its receptors in myocardial ischemia/reperfusion injury and cardioprotection |
| publisher |
Frontiers Media S.A. |
| publishDate |
2021 |
| url |
https://doaj.org/article/dcbc88f896f543ad8ae2da1ca762c860 |
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