Kynurenic Acid: A Novel Player in Cardioprotection against Myocardial Ischemia/Reperfusion Injuries
Background: Myocardial infarction is one of the leading causes of mortality worldwide; hence, there is an urgent need to discover novel cardioprotective strategies. Kynurenic acid (KYNA), a metabolite of the kynurenine pathway, has been previously reported to have cardioprotective effects. However,...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-09-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/16/10/1381 |
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| author | Rima Kamel Delphine Baetz Naïg Gueguen Lucie Lebeau Agnès Barbelivien Anne-Laure Guihot Louwana Allawa Jean Gallet Justine Beaumont Michel Ovize Daniel Henrion Pascal Reynier Delphine Mirebeau-Prunier Fabrice Prunier Sophie Tamareille |
| author_facet | Rima Kamel Delphine Baetz Naïg Gueguen Lucie Lebeau Agnès Barbelivien Anne-Laure Guihot Louwana Allawa Jean Gallet Justine Beaumont Michel Ovize Daniel Henrion Pascal Reynier Delphine Mirebeau-Prunier Fabrice Prunier Sophie Tamareille |
| author_sort | Rima Kamel |
| collection | DOAJ |
| description | Background: Myocardial infarction is one of the leading causes of mortality worldwide; hence, there is an urgent need to discover novel cardioprotective strategies. Kynurenic acid (KYNA), a metabolite of the kynurenine pathway, has been previously reported to have cardioprotective effects. However, the mechanisms by which KYNA may be protective are still unclear. The current study addressed this issue by investigating KYNA’s cardioprotective effect in the context of myocardial ischemia/reperfusion. Methods: H9C2 cells and rats were exposed to hypoxia/reoxygenation or myocardial infarction, respectively, in the presence or absence of KYNA. In vitro, cell death was quantified using flow cytometry analysis of propidium iodide staining. In vivo, TTC-Evans Blue staining was performed to evaluate infarct size. Mitochondrial respiratory chain complex activities were measured using spectrophotometry. Protein expression was evaluated by Western blot, and mRNA levels by RT-qPCR. Results: KYNA treatment significantly reduced H9C2-relative cell death as well as infarct size. KYNA did not exhibit any effect on the mitochondrial respiratory chain complex activity. SOD2 mRNA levels were increased by KYNA. A decrease in p62 protein levels together with a trend of increase in PARK2 may mark a stimulation of mitophagy. Additionally, ERK1/2, Akt, and FOXO3α phosphorylation levels were significantly reduced after the KYNA treatment. Altogether, KYNA significantly reduced myocardial ischemia/reperfusion injuries in both in vitro and in vivo models. Conclusion: Here we show that KYNA-mediated cardioprotection was associated with enhanced mitophagy and antioxidant defense. A deeper understanding of KYNA’s cardioprotective mechanisms is necessary to identify promising novel therapeutic targets and their translation into the clinical arena. |
| first_indexed | 2024-03-10T20:58:51Z |
| format | Article |
| id | doaj.art-91b3b2d082cb42b18d3431735fe784c8 |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-10T20:58:51Z |
| publishDate | 2023-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-91b3b2d082cb42b18d3431735fe784c82023-11-19T17:41:41ZengMDPI AGPharmaceuticals1424-82472023-09-011610138110.3390/ph16101381Kynurenic Acid: A Novel Player in Cardioprotection against Myocardial Ischemia/Reperfusion InjuriesRima Kamel0Delphine Baetz1Naïg Gueguen2Lucie Lebeau3Agnès Barbelivien4Anne-Laure Guihot5Louwana Allawa6Jean Gallet7Justine Beaumont8Michel Ovize9Daniel Henrion10Pascal Reynier11Delphine Mirebeau-Prunier12Fabrice Prunier13Sophie Tamareille14MITOVASC, SFR ICAT, CNRS 6015, INSERM U1083, Université d’Angers, F-49000 Angers, FranceLaboratoire CarMeN, INSERM U1060, INRA U1397, Université Claude Bernard Lyon 1, F-69500 Bron, FranceMITOVASC, SFR ICAT, CNRS 6015, INSERM U1083, Université d’Angers, F-49000 Angers, FranceMITOVASC, SFR ICAT, CNRS 6015, INSERM U1083, Université d’Angers, F-49000 Angers, FranceMITOVASC, SFR ICAT, CNRS 6015, INSERM U1083, Université d’Angers, F-49000 Angers, FranceMITOVASC, SFR ICAT, CNRS 6015, INSERM U1083, Université d’Angers, F-49000 Angers, FranceMITOVASC, SFR ICAT, CNRS 6015, INSERM U1083, Université d’Angers, F-49000 Angers, FranceService de Cardiologie, CHU Angers, F-49000 Angers, FranceMITOVASC, SFR ICAT, CNRS 6015, INSERM U1083, Université d’Angers, F-49000 Angers, FranceLaboratoire CarMeN, INSERM U1060, INRA U1397, Université Claude Bernard Lyon 1, F-69500 Bron, FranceMITOVASC, SFR ICAT, CNRS 6015, INSERM U1083, Université d’Angers, F-49000 Angers, FranceMITOVASC, SFR ICAT, CNRS 6015, INSERM U1083, Université d’Angers, F-49000 Angers, FranceMITOVASC, SFR ICAT, CNRS 6015, INSERM U1083, Université d’Angers, F-49000 Angers, FranceMITOVASC, SFR ICAT, CNRS 6015, INSERM U1083, Université d’Angers, F-49000 Angers, FranceMITOVASC, SFR ICAT, CNRS 6015, INSERM U1083, Université d’Angers, F-49000 Angers, FranceBackground: Myocardial infarction is one of the leading causes of mortality worldwide; hence, there is an urgent need to discover novel cardioprotective strategies. Kynurenic acid (KYNA), a metabolite of the kynurenine pathway, has been previously reported to have cardioprotective effects. However, the mechanisms by which KYNA may be protective are still unclear. The current study addressed this issue by investigating KYNA’s cardioprotective effect in the context of myocardial ischemia/reperfusion. Methods: H9C2 cells and rats were exposed to hypoxia/reoxygenation or myocardial infarction, respectively, in the presence or absence of KYNA. In vitro, cell death was quantified using flow cytometry analysis of propidium iodide staining. In vivo, TTC-Evans Blue staining was performed to evaluate infarct size. Mitochondrial respiratory chain complex activities were measured using spectrophotometry. Protein expression was evaluated by Western blot, and mRNA levels by RT-qPCR. Results: KYNA treatment significantly reduced H9C2-relative cell death as well as infarct size. KYNA did not exhibit any effect on the mitochondrial respiratory chain complex activity. SOD2 mRNA levels were increased by KYNA. A decrease in p62 protein levels together with a trend of increase in PARK2 may mark a stimulation of mitophagy. Additionally, ERK1/2, Akt, and FOXO3α phosphorylation levels were significantly reduced after the KYNA treatment. Altogether, KYNA significantly reduced myocardial ischemia/reperfusion injuries in both in vitro and in vivo models. Conclusion: Here we show that KYNA-mediated cardioprotection was associated with enhanced mitophagy and antioxidant defense. A deeper understanding of KYNA’s cardioprotective mechanisms is necessary to identify promising novel therapeutic targets and their translation into the clinical arena.https://www.mdpi.com/1424-8247/16/10/1381kynurenic acidmyocardial infarctioncardioprotectionmitophagyoxidative stresskynurenine pathway |
| spellingShingle | Rima Kamel Delphine Baetz Naïg Gueguen Lucie Lebeau Agnès Barbelivien Anne-Laure Guihot Louwana Allawa Jean Gallet Justine Beaumont Michel Ovize Daniel Henrion Pascal Reynier Delphine Mirebeau-Prunier Fabrice Prunier Sophie Tamareille Kynurenic Acid: A Novel Player in Cardioprotection against Myocardial Ischemia/Reperfusion Injuries Pharmaceuticals kynurenic acid myocardial infarction cardioprotection mitophagy oxidative stress kynurenine pathway |
| title | Kynurenic Acid: A Novel Player in Cardioprotection against Myocardial Ischemia/Reperfusion Injuries |
| title_full | Kynurenic Acid: A Novel Player in Cardioprotection against Myocardial Ischemia/Reperfusion Injuries |
| title_fullStr | Kynurenic Acid: A Novel Player in Cardioprotection against Myocardial Ischemia/Reperfusion Injuries |
| title_full_unstemmed | Kynurenic Acid: A Novel Player in Cardioprotection against Myocardial Ischemia/Reperfusion Injuries |
| title_short | Kynurenic Acid: A Novel Player in Cardioprotection against Myocardial Ischemia/Reperfusion Injuries |
| title_sort | kynurenic acid a novel player in cardioprotection against myocardial ischemia reperfusion injuries |
| topic | kynurenic acid myocardial infarction cardioprotection mitophagy oxidative stress kynurenine pathway |
| url | https://www.mdpi.com/1424-8247/16/10/1381 |
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