'' Non alcoholic fatty liver disease and eNOS dysfunction in humans ''


Persico, Marcello, Masarone, Mario, Damato, Antonio, Ambrosio, Mariateresa, Federico, Alessandro, Rosato, Valerio, Bucci, Tommaso ORCID: 0000-0003-2895-6234, Carrizzo, Albino and Vecchione, Carmine (2017) '' Non alcoholic fatty liver disease and eNOS dysfunction in humans ''. BMC GASTROENTEROLOGY, 17 (1). 35-.

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Abstract

Background NAFLD is associated to Insulin Resistance (IR). IR is responsible for Endothelial Dysfunction (ED) through the impairment of eNOS function. Although eNOS derangement has been demonstrated in experimental models, no studies have directly shown that eNOS dysfunction is associated with NAFLD in humans. The aim of this study is to investigate eNOS function in NAFLD patients. Methods Fifty-four NAFLD patients were consecutively enrolled. All patients underwent clinical and laboratory evaluation and liver biopsy. Patients were divided into two groups by the presence of NAFL or NASH. We measured vascular reactivity induced by patients’ platelets on isolated mice aorta rings. Immunoblot assays for platelet-derived phosphorylated-eNOS (p-eNOS) and immunohistochemistry for hepatic p-eNOS have been performed to evaluate eNOS function in platelets and liver specimens. Flow-mediated-dilation (FMD) was also performed. Data were compared with healthy controls. Results Twenty-one (38, 8%) patients had NAFL and 33 (61, 7%) NASH. No differences were found between groups and controls except for HOMA and insulin (p < 0.0001). Vascular reactivity demonstrated a reduced function induced from NAFLD platelets as compared with controls (p < 0.001), associated with an impaired p-eNOS in both platelets and liver (p < 0.001). NAFL showed a higher impairment of eNOS phosphorylation in comparison to NASH (p < 0.01). In contrast with what observed in vitro, the vascular response by FMD was worse in NASH as compared with NAFL. Conclusions Our data showed, for the first time in humans, that NAFLD patients show a marked eNOS dysfunction, which may contribute to a higher CV risk. eNOS dysfunction observed in platelets and liver tissue didn’t match with FMD.

Item Type: Article
Uncontrolled Keywords: Endothelial dysfunction, Insulin resistance, Metabolic syndrome, Non-alcoholic fatty liver disease
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Life Courses and Medical Sciences
Depositing User: Symplectic Admin
Date Deposited: 17 Aug 2022 12:24
Last Modified: 11 Oct 2023 12:27
DOI: 10.1186/s12876-017-0592-y
Open Access URL: https://bmcgastroenterol.biomedcentral.com/article...
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3161466

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