“Non alcoholic fatty liver disease and eNOS dysfunction in humans”

BMC Gastroenterology

Research Article

Carmine Vecchione¹  Alessandro Federico²  Valerio Rosato³  Tommaso Bucci⁴  Marcello Persico⁴  Mario Masarone⁴  Mariateresa Ambrosio⁵  Antonio Damato⁵  Albino Carrizzo⁵ 

[1] Department of Medicine and Surgery, University of Salerno, Salerno, Italy;Hepato-Gastroenterology Division, University of Campania “L. Vanvitelli”, Naples, Italy;Internal Medicine and Hepatology Department, University of Campania “L. Vanvitelli”, Naples, Italy;Internal Medicine and Hepatology Unit, PO G. Da Procida—AOU- San Giovanni e Ruggi D’Aragona, University of Salerno, Via Salvatore Calenda 162, CAP: 84126, Salerno, Italy;Vascular Physiopathology Unit IRCCS, INM Neuromed, Pozzilli, IS, Italy;

关键词: Non-alcoholic fatty liver disease;    Endothelial dysfunction;    Metabolic syndrome;    Insulin resistance;   

DOI  :  10.1186/s12876-017-0592-y

 received in 2016-10-09, accepted in 2017-03-01,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundNAFLD 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.MethodsFifty-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.ResultsTwenty-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.ConclusionsOur 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.

【 授权许可】

CC BY   
© The Author(s). 2017