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Potential Role of Lisinopril in Reducing Atherosclerotic Risk: Evidence of an Antioxidant Effect in Human Cardiomyocytes Cell Line
The cellular mechanisms involved in myocardial ischemia/reperfusion injury (I/R) pathogenesis are complex but attributable to reactive oxygen species (ROS) production. ROS produced by coronary endothelial cells, blood cells (e.g., leukocytes and platelets), and cardiac myocytes have the potential to...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9152216/ https://www.ncbi.nlm.nih.gov/pubmed/35656292 http://dx.doi.org/10.3389/fphar.2022.868365 |
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author | Scisciola, Lucia Fontanella, Rosaria Anna Surina, Garofalo, Giovanna Rizzo, Maria Rosaria Paolisso, Giuseppe Barbieri, Michelangela |
author_facet | Scisciola, Lucia Fontanella, Rosaria Anna Surina, Garofalo, Giovanna Rizzo, Maria Rosaria Paolisso, Giuseppe Barbieri, Michelangela |
author_sort | Scisciola, Lucia |
collection | PubMed |
description | The cellular mechanisms involved in myocardial ischemia/reperfusion injury (I/R) pathogenesis are complex but attributable to reactive oxygen species (ROS) production. ROS produced by coronary endothelial cells, blood cells (e.g., leukocytes and platelets), and cardiac myocytes have the potential to damage vascular cells directly and cardiac myocytes, initiating mechanisms that induce apoptosis, inflammation, necrosis, and fibrosis of myocardial cells. In addition to reducing blood pressure, lisinopril, a new non-sulfhydryl angiotensin-converting enzyme (ACE) inhibitor, increases the antioxidant defense in animals and humans. Recently, it has been shown that lisinopril can attenuate renal oxidative injury in the l-NAME-induced hypertensive rat and cause an impressive improvement in the antioxidant defense system of Wistar rats treated with doxorubicin. The potential effect of lisinopril on oxidative damage and fibrosis in human cardiomyocytes has not been previously investigated. Thus, the present study aims to investigate the effect of different doses of lisinopril on oxidative stress and fibrotic mediators in AC16 human cardiomyocytes, along with a 7-day presence in the culture medium. The results revealed that AC16 human cardiomyocytes exposed to lisinopril treatment significantly showed an upregulation of proteins involved in protecting against oxidative stress, such as catalase, SOD2, and thioredoxin, and a reduction of osteopontin and Galectin-3, critical proteins involved in cardiac fibrosis. Moreover, lisinopril treatment induced an increment in Sirtuin 1 and Sirtuin 6 protein expression. These findings demonstrated that, in AC16 human cardiomyocytes, lisinopril could protect against oxidative stress and fibrosis via the activation of Sirtuin 1 and Sirtuin 6 pathways. |
format | Online Article Text |
id | pubmed-9152216 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-91522162022-06-01 Potential Role of Lisinopril in Reducing Atherosclerotic Risk: Evidence of an Antioxidant Effect in Human Cardiomyocytes Cell Line Scisciola, Lucia Fontanella, Rosaria Anna Surina, Garofalo, Giovanna Rizzo, Maria Rosaria Paolisso, Giuseppe Barbieri, Michelangela Front Pharmacol Pharmacology The cellular mechanisms involved in myocardial ischemia/reperfusion injury (I/R) pathogenesis are complex but attributable to reactive oxygen species (ROS) production. ROS produced by coronary endothelial cells, blood cells (e.g., leukocytes and platelets), and cardiac myocytes have the potential to damage vascular cells directly and cardiac myocytes, initiating mechanisms that induce apoptosis, inflammation, necrosis, and fibrosis of myocardial cells. In addition to reducing blood pressure, lisinopril, a new non-sulfhydryl angiotensin-converting enzyme (ACE) inhibitor, increases the antioxidant defense in animals and humans. Recently, it has been shown that lisinopril can attenuate renal oxidative injury in the l-NAME-induced hypertensive rat and cause an impressive improvement in the antioxidant defense system of Wistar rats treated with doxorubicin. The potential effect of lisinopril on oxidative damage and fibrosis in human cardiomyocytes has not been previously investigated. Thus, the present study aims to investigate the effect of different doses of lisinopril on oxidative stress and fibrotic mediators in AC16 human cardiomyocytes, along with a 7-day presence in the culture medium. The results revealed that AC16 human cardiomyocytes exposed to lisinopril treatment significantly showed an upregulation of proteins involved in protecting against oxidative stress, such as catalase, SOD2, and thioredoxin, and a reduction of osteopontin and Galectin-3, critical proteins involved in cardiac fibrosis. Moreover, lisinopril treatment induced an increment in Sirtuin 1 and Sirtuin 6 protein expression. These findings demonstrated that, in AC16 human cardiomyocytes, lisinopril could protect against oxidative stress and fibrosis via the activation of Sirtuin 1 and Sirtuin 6 pathways. Frontiers Media S.A. 2022-05-17 /pmc/articles/PMC9152216/ /pubmed/35656292 http://dx.doi.org/10.3389/fphar.2022.868365 Text en Copyright © 2022 Scisciola, Fontanella, Surina, Garofalo, Rizzo, Paolisso and Barbieri. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Pharmacology Scisciola, Lucia Fontanella, Rosaria Anna Surina, Garofalo, Giovanna Rizzo, Maria Rosaria Paolisso, Giuseppe Barbieri, Michelangela Potential Role of Lisinopril in Reducing Atherosclerotic Risk: Evidence of an Antioxidant Effect in Human Cardiomyocytes Cell Line |
title | Potential Role of Lisinopril in Reducing Atherosclerotic Risk: Evidence of an Antioxidant Effect in Human Cardiomyocytes Cell Line |
title_full | Potential Role of Lisinopril in Reducing Atherosclerotic Risk: Evidence of an Antioxidant Effect in Human Cardiomyocytes Cell Line |
title_fullStr | Potential Role of Lisinopril in Reducing Atherosclerotic Risk: Evidence of an Antioxidant Effect in Human Cardiomyocytes Cell Line |
title_full_unstemmed | Potential Role of Lisinopril in Reducing Atherosclerotic Risk: Evidence of an Antioxidant Effect in Human Cardiomyocytes Cell Line |
title_short | Potential Role of Lisinopril in Reducing Atherosclerotic Risk: Evidence of an Antioxidant Effect in Human Cardiomyocytes Cell Line |
title_sort | potential role of lisinopril in reducing atherosclerotic risk: evidence of an antioxidant effect in human cardiomyocytes cell line |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9152216/ https://www.ncbi.nlm.nih.gov/pubmed/35656292 http://dx.doi.org/10.3389/fphar.2022.868365 |
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