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

Autor: Mona Isabella Benker, Paige Brlecic, Sivakkanan Loganathan, Patricia Kraft, Tamás Radovits, Sevil Korkmaz-Icöz, Alex Ali Sayour, Sophia Abulizi, Matthias Karck, Adrian-Iustin Georgevici, Gábor Szabó, Cenk Kocer
Jazyk: angličtina
Rok vydání: 2021
Předmět:
0301 basic medicine
Male
medicine.medical_treatment
030204 cardiovascular system & hematology
chemistry.chemical_compound
0302 clinical medicine
endothelial function
Medicine
Endothelial dysfunction
Biology (General)
canagliflozin
Saline
Spectroscopy
Canagliflozin
Neovascularization
Pathologic
Nitrotyrosine
General Medicine
Computer Science Applications
Vasodilation
Chemistry
medicine.anatomical_structure
Sodium/Glucose Cotransporter 2
Reperfusion Injury
diabetes mellitus
Artery
medicine.drug
medicine.medical_specialty
QH301-705.5
sodium-glucose cotransporter-2
CCL4
In Vitro Techniques
Catalysis
Article
Inorganic Chemistry
03 medical and health sciences
Internal medicine
Animals
Vascular Diseases
Physical and Theoretical Chemistry
Rats
Wistar
Molecular Biology
Sodium-Glucose Transporter 2 Inhibitors
QD1-999
business.industry
Organic Chemistry
medicine.disease
ischemia/reperfusion
Rats
030104 developmental biology
Endocrinology
chemistry
Endothelium
Vascular
business
Reperfusion injury
Zdroj: International Journal of Molecular Sciences, Vol 22, Iss 7774, p 7774 (2021)
International Journal of Molecular Sciences
Volume 22
Issue 15
ISSN: 1661-6596
1422-0067
Popis: 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.
Databáze: OpenAIRE
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