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

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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Published in:International journal of molecular sciences Vol. 22; no. 15; p. 7774
Main Authors: 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
Format: Journal Article
Language:English
Published: Basel MDPI AG 01-08-2021
MDPI
Subjects:
Acetylcholine
Algorithms
Antidiabetics
Aorta
Apoptosis
canagliflozin
CCL3 protein
CD31 antigen
CD40 antigen
Chemokines
Clinical outcomes
Coronary artery
Coronary vessels
Cryopreservation
CXCR4 protein
Diabetes
Diabetes mellitus
endothelial function
Endothelium
Gene expression
Genes
Glucose
Graft rejection
Grafting
Grafts
IL-1β
Immunoreactivity
Inhibitors
Intercellular adhesion molecule 1
Interleukin 1
Interleukin 10
Interleukin 6
Ischemia
ischemia/reperfusion
Learning algorithms
Monocyte chemoattractant protein 1
Nitric oxide
Nitrotyrosine
Oxidative stress
Pathophysiology
Physiology
Reperfusion
Smooth muscle
Sodium
sodium-glucose cotransporter-2
Vasodilation
Veins & arteries
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Summary: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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ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms22157774