The Rationale of Neprilysin Inhibition in Prevention of Myocardial Ischemia-Reperfusion Injury during ST-Elevation Myocardial Infarction
During the last three decades, timely myocardial reperfusion using either thrombolytic therapy or primary percutaneous intervention (pPCI) has allowed amazing improvements in outcomes with a more than halving in 1-year ST-elevation myocardial infarction (STEMI) mortality. However, mortality and left...
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| Format: | Article |
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MDPI AG
2020-09-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/9/9/2134 |
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| author | Alessandro Bellis Ciro Mauro Emanuele Barbato Giuseppe Di Gioia Daniela Sorriento Bruno Trimarco Carmine Morisco |
| author_facet | Alessandro Bellis Ciro Mauro Emanuele Barbato Giuseppe Di Gioia Daniela Sorriento Bruno Trimarco Carmine Morisco |
| author_sort | Alessandro Bellis |
| collection | DOAJ |
| description | During the last three decades, timely myocardial reperfusion using either thrombolytic therapy or primary percutaneous intervention (pPCI) has allowed amazing improvements in outcomes with a more than halving in 1-year ST-elevation myocardial infarction (STEMI) mortality. However, mortality and left ventricle (LV) remodeling remain substantial in these patients. As such, novel therapeutic interventions are required to reduce myocardial infarction size, preserve LV systolic function, and improve survival in reperfused-STEMI patients. Myocardial ischemia-reperfusion injury (MIRI) prevention represents the main goal to reach in order to reduce STEMI mortality. There is currently no effective therapy for MIRI prevention in STEMI patients. A significant reason for the weak and inconsistent results obtained in this field may be the presence of multiple, partially redundant, mechanisms of cell death during ischemia-reperfusion, whose relative importance may depend on the conditions. Therefore, it is always more recognized that it is important to consider a “multi-targeted cardioprotective therapy”, defined as an additive or synergistic cardioprotective agents or interventions directed to distinct targets with different timing of application (before, during, or after pPCI). Given that some neprilysin (NEP) substrates (natriuretic peptides, angiotensin II, bradykinin, apelins, substance P, and adrenomedullin) exert a cardioprotective effect against ischemia-reperfusion injury, it is conceivable that antagonism of proteolytic activity by this enzyme may be considered in a multi-targeted strategy for MIRI prevention. In this review, by starting from main pathophysiological mechanisms promoting MIRI, we discuss cardioprotective effects of NEP substrates and the potential benefit of NEP pharmacological inhibition in MIRI prevention. |
| first_indexed | 2024-03-10T16:09:46Z |
| format | Article |
| id | doaj.art-7d2001ddfb4f4534827145241ad3ed59 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T16:09:46Z |
| publishDate | 2020-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-7d2001ddfb4f4534827145241ad3ed592023-11-20T14:34:11ZengMDPI AGCells2073-44092020-09-0199213410.3390/cells9092134The Rationale of Neprilysin Inhibition in Prevention of Myocardial Ischemia-Reperfusion Injury during ST-Elevation Myocardial InfarctionAlessandro Bellis0Ciro Mauro1Emanuele Barbato2Giuseppe Di Gioia3Daniela Sorriento4Bruno Trimarco5Carmine Morisco6Dipartimento di Scienze Biomediche Avanzate, Università FEDERICO II, 80131 Napoli, ItalyUnità Operativa Complessa Cardiologia con UTIC ed Emodinamica—Dipartimento Emergenza Accettazione, Azienda Ospedaliera “Antonio Cardarelli”, 80131 Napoli, ItalyDipartimento di Scienze Biomediche Avanzate, Università FEDERICO II, 80131 Napoli, ItalyDipartimento di Scienze Biomediche Avanzate, Università FEDERICO II, 80131 Napoli, ItalyDipartimento di Scienze Biomediche Avanzate, Università FEDERICO II, 80131 Napoli, ItalyDipartimento di Scienze Biomediche Avanzate, Università FEDERICO II, 80131 Napoli, ItalyDipartimento di Scienze Biomediche Avanzate, Università FEDERICO II, 80131 Napoli, ItalyDuring the last three decades, timely myocardial reperfusion using either thrombolytic therapy or primary percutaneous intervention (pPCI) has allowed amazing improvements in outcomes with a more than halving in 1-year ST-elevation myocardial infarction (STEMI) mortality. However, mortality and left ventricle (LV) remodeling remain substantial in these patients. As such, novel therapeutic interventions are required to reduce myocardial infarction size, preserve LV systolic function, and improve survival in reperfused-STEMI patients. Myocardial ischemia-reperfusion injury (MIRI) prevention represents the main goal to reach in order to reduce STEMI mortality. There is currently no effective therapy for MIRI prevention in STEMI patients. A significant reason for the weak and inconsistent results obtained in this field may be the presence of multiple, partially redundant, mechanisms of cell death during ischemia-reperfusion, whose relative importance may depend on the conditions. Therefore, it is always more recognized that it is important to consider a “multi-targeted cardioprotective therapy”, defined as an additive or synergistic cardioprotective agents or interventions directed to distinct targets with different timing of application (before, during, or after pPCI). Given that some neprilysin (NEP) substrates (natriuretic peptides, angiotensin II, bradykinin, apelins, substance P, and adrenomedullin) exert a cardioprotective effect against ischemia-reperfusion injury, it is conceivable that antagonism of proteolytic activity by this enzyme may be considered in a multi-targeted strategy for MIRI prevention. In this review, by starting from main pathophysiological mechanisms promoting MIRI, we discuss cardioprotective effects of NEP substrates and the potential benefit of NEP pharmacological inhibition in MIRI prevention.https://www.mdpi.com/2073-4409/9/9/2134neprilysinmyocardial ischemia-reperfusion injurynatriuretic peptideangiotensin IIbradykininapelin |
| spellingShingle | Alessandro Bellis Ciro Mauro Emanuele Barbato Giuseppe Di Gioia Daniela Sorriento Bruno Trimarco Carmine Morisco The Rationale of Neprilysin Inhibition in Prevention of Myocardial Ischemia-Reperfusion Injury during ST-Elevation Myocardial Infarction Cells neprilysin myocardial ischemia-reperfusion injury natriuretic peptide angiotensin II bradykinin apelin |
| title | The Rationale of Neprilysin Inhibition in Prevention of Myocardial Ischemia-Reperfusion Injury during ST-Elevation Myocardial Infarction |
| title_full | The Rationale of Neprilysin Inhibition in Prevention of Myocardial Ischemia-Reperfusion Injury during ST-Elevation Myocardial Infarction |
| title_fullStr | The Rationale of Neprilysin Inhibition in Prevention of Myocardial Ischemia-Reperfusion Injury during ST-Elevation Myocardial Infarction |
| title_full_unstemmed | The Rationale of Neprilysin Inhibition in Prevention of Myocardial Ischemia-Reperfusion Injury during ST-Elevation Myocardial Infarction |
| title_short | The Rationale of Neprilysin Inhibition in Prevention of Myocardial Ischemia-Reperfusion Injury during ST-Elevation Myocardial Infarction |
| title_sort | rationale of neprilysin inhibition in prevention of myocardial ischemia reperfusion injury during st elevation myocardial infarction |
| topic | neprilysin myocardial ischemia-reperfusion injury natriuretic peptide angiotensin II bradykinin apelin |
| url | https://www.mdpi.com/2073-4409/9/9/2134 |
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