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The Sodium-Glucose Cotransporter-2 Inhibitor Canagliflozin Alleviates Endothelial Dysfunction Following In Vitro Vascular Ischemia/Reperfusion Injury in Rats

Vascular ischemia/reperfusion injury (IRI) contributes to graft failure and adverse clinical outcomes following coronary artery bypass grafting. Sodium-glucose-cotransporter (SGLT)-2-inhibitors have been shown to protect against myocardial IRI, irrespective of diabetes. We hypothesized that adding c...

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Autores principales: Korkmaz-Icöz, Sevil, Kocer, Cenk, Sayour, Alex A., Kraft, Patricia, Benker, Mona I., Abulizi, Sophia, Georgevici, Adrian-Iustin, Brlecic, Paige, Radovits, Tamás, Loganathan, Sivakkanan, Karck, Matthias, Szabó, Gábor
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8345991/
https://www.ncbi.nlm.nih.gov/pubmed/34360539
http://dx.doi.org/10.3390/ijms22157774
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author Korkmaz-Icöz, Sevil
Kocer, Cenk
Sayour, Alex A.
Kraft, Patricia
Benker, Mona I.
Abulizi, Sophia
Georgevici, Adrian-Iustin
Brlecic, Paige
Radovits, Tamás
Loganathan, Sivakkanan
Karck, Matthias
Szabó, Gábor
author_facet Korkmaz-Icöz, Sevil
Kocer, Cenk
Sayour, Alex A.
Kraft, Patricia
Benker, Mona I.
Abulizi, Sophia
Georgevici, Adrian-Iustin
Brlecic, Paige
Radovits, Tamás
Loganathan, Sivakkanan
Karck, Matthias
Szabó, Gábor
author_sort Korkmaz-Icöz, Sevil
collection PubMed
description Vascular ischemia/reperfusion injury (IRI) contributes to graft failure and adverse clinical outcomes following coronary artery bypass grafting. Sodium-glucose-cotransporter (SGLT)-2-inhibitors have been shown to protect against myocardial IRI, irrespective of diabetes. We hypothesized that adding canagliflozin (CANA) (an SGLT-2-inhibitor) to saline protects vascular grafts from IRI. Aortic rings from non-diabetic rats were isolated and immediately mounted in organ bath chambers (control, n = 9–10 rats) or underwent cold ischemic preservation in saline, supplemented either with a DMSO vehicle (IR, n = 8–10 rats) or 50µM CANA (IR + CANA, n = 9–11 rats). Vascular function was measured, the expression of 88 genes using PCR-array was analyzed, and feature selection using machine learning was applied. Impaired maximal vasorelaxation to acetylcholine in the IR-group compared to controls was significantly ameliorated by CANA (IR 31.7 ± 3.2% vs. IR + CANA 51.9 ± 2.5%, p < 0.05). IR altered the expression of 17 genes. Ccl2, Ccl3, Ccl4, CxCr4, Fos, Icam1, Il10, Il1a and Il1b have been found to have the highest interaction. Compared to controls, IR significantly upregulated the mRNA expressions of Il1a and Il6, which were reduced by 1.5- and 1.75-fold with CANA, respectively. CANA significantly prevented the upregulation of Cd40, downregulated NoxO1 gene expression, decreased ICAM-1 and nitrotyrosine, and increased PECAM-1 immunoreactivity. CANA alleviates endothelial dysfunction following IRI.
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spelling pubmed-83459912021-08-07 The Sodium-Glucose Cotransporter-2 Inhibitor Canagliflozin Alleviates Endothelial Dysfunction Following In Vitro Vascular Ischemia/Reperfusion Injury in Rats Korkmaz-Icöz, Sevil Kocer, Cenk Sayour, Alex A. Kraft, Patricia Benker, Mona I. Abulizi, Sophia Georgevici, Adrian-Iustin Brlecic, Paige Radovits, Tamás Loganathan, Sivakkanan Karck, Matthias Szabó, Gábor Int J Mol Sci Article Vascular ischemia/reperfusion injury (IRI) contributes to graft failure and adverse clinical outcomes following coronary artery bypass grafting. Sodium-glucose-cotransporter (SGLT)-2-inhibitors have been shown to protect against myocardial IRI, irrespective of diabetes. We hypothesized that adding canagliflozin (CANA) (an SGLT-2-inhibitor) to saline protects vascular grafts from IRI. Aortic rings from non-diabetic rats were isolated and immediately mounted in organ bath chambers (control, n = 9–10 rats) or underwent cold ischemic preservation in saline, supplemented either with a DMSO vehicle (IR, n = 8–10 rats) or 50µM CANA (IR + CANA, n = 9–11 rats). Vascular function was measured, the expression of 88 genes using PCR-array was analyzed, and feature selection using machine learning was applied. Impaired maximal vasorelaxation to acetylcholine in the IR-group compared to controls was significantly ameliorated by CANA (IR 31.7 ± 3.2% vs. IR + CANA 51.9 ± 2.5%, p < 0.05). IR altered the expression of 17 genes. Ccl2, Ccl3, Ccl4, CxCr4, Fos, Icam1, Il10, Il1a and Il1b have been found to have the highest interaction. Compared to controls, IR significantly upregulated the mRNA expressions of Il1a and Il6, which were reduced by 1.5- and 1.75-fold with CANA, respectively. CANA significantly prevented the upregulation of Cd40, downregulated NoxO1 gene expression, decreased ICAM-1 and nitrotyrosine, and increased PECAM-1 immunoreactivity. CANA alleviates endothelial dysfunction following IRI. MDPI 2021-07-21 /pmc/articles/PMC8345991/ /pubmed/34360539 http://dx.doi.org/10.3390/ijms22157774 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Korkmaz-Icöz, Sevil
Kocer, Cenk
Sayour, Alex A.
Kraft, Patricia
Benker, Mona I.
Abulizi, Sophia
Georgevici, Adrian-Iustin
Brlecic, Paige
Radovits, Tamás
Loganathan, Sivakkanan
Karck, Matthias
Szabó, Gábor
The Sodium-Glucose Cotransporter-2 Inhibitor Canagliflozin Alleviates Endothelial Dysfunction Following In Vitro Vascular Ischemia/Reperfusion Injury in Rats
title The Sodium-Glucose Cotransporter-2 Inhibitor Canagliflozin Alleviates Endothelial Dysfunction Following In Vitro Vascular Ischemia/Reperfusion Injury in Rats
title_full The Sodium-Glucose Cotransporter-2 Inhibitor Canagliflozin Alleviates Endothelial Dysfunction Following In Vitro Vascular Ischemia/Reperfusion Injury in Rats
title_fullStr The Sodium-Glucose Cotransporter-2 Inhibitor Canagliflozin Alleviates Endothelial Dysfunction Following In Vitro Vascular Ischemia/Reperfusion Injury in Rats
title_full_unstemmed The Sodium-Glucose Cotransporter-2 Inhibitor Canagliflozin Alleviates Endothelial Dysfunction Following In Vitro Vascular Ischemia/Reperfusion Injury in Rats
title_short The Sodium-Glucose Cotransporter-2 Inhibitor Canagliflozin Alleviates Endothelial Dysfunction Following In Vitro Vascular Ischemia/Reperfusion Injury in Rats
title_sort sodium-glucose cotransporter-2 inhibitor canagliflozin alleviates endothelial dysfunction following in vitro vascular ischemia/reperfusion injury in rats
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8345991/
https://www.ncbi.nlm.nih.gov/pubmed/34360539
http://dx.doi.org/10.3390/ijms22157774
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