Faculty Collaboration Database

Vascular endothelial growth factor regulation of endothelial nitric oxide synthase phosphorylation is involved in isoflurane cardiac preconditioning. Cardiovasc Res 2019 Jan 01;115(1):168-178

Date

06/23/2018

Pubmed ID

29931049

Pubmed Central ID

PMC6302266

DOI

10.1093/cvr/cvy157

Scopus ID

2-s2.0-85058917907 (requires institutional sign-in at Scopus site)   28 Citations

Abstract

AIMS: Previous studies indicate that nitric oxide derived from endothelial nitric oxide synthase (eNOS) serves as both trigger and mediator in anaesthetic cardiac preconditioning. The mechanisms underlying regulation of eNOS by volatile anaesthetics have not been fully understood. Therefore, this study examined the role of vascular endothelial growth factor (VEGF) in isoflurane cardiac preconditioning.

METHODS AND RESULTS: Wistar rats underwent 30 min of coronary artery occlusion followed by 2 h of reperfusion. Isoflurane given prior to ischaemia/reperfusion significantly decreased myocardial infarct size from 60 ± 1% in control to 40 ± 3% (n = 8 rats/group, P < 0.05). The beneficial effects of isoflurane were blocked by neutralizing antibody against VEGF (nVEGF). Coronary arterial endothelial cells (ECs) alone or together with cardiomyocytes (CMs) were subjected to hypoxia/reoxygenation injury. The expression of VEGF and eNOS was analysed by western blot, and nitric oxide was measured by ozone-based chemiluminescence. In co-cultured CMs and ECs, isoflurane administered before hypoxia/reoxygenation attenuated lactate dehydrogenase activity and increased the ratio of phosphorylated eNOS/eNOS and nitric oxide production. The protective effect of isoflurane on CMs was compromised by nVEGF and after VEGF in ECs was inhibited with hypoxia inducible factor-1α short hairpin RNA (shRNA). The negative effect of hypoxia inducible factor-1α shRNA was restored by recombinant VEGF.

CONCLUSION: Isoflurane cardiac preconditioning is associated with VEGF regulation of phosphorylation of eNOS and nitric oxide production.

Author List

Liu Y, Paterson M, Baumgardt SL, Irwin MG, Xia Z, Bosnjak ZJ, Ge ZD

MESH terms used to index this publication - Major topics in bold

Animals
Cell Communication
Cells, Cultured
Coculture Techniques
Disease Models, Animal
Endothelial Cells
Female
Humans
Hypoxia-Inducible Factor 1, alpha Subunit
Ischemic Preconditioning, Myocardial
Isoflurane
Male
Myocardial Reperfusion Injury
Myocytes, Cardiac
Nitric Oxide Synthase Type III
Phosphorylation
Rats, Wistar
Signal Transduction
Vascular Endothelial Growth Factor A