title: "Non alcoholic fatty liver disease and eNOS dysfunction in humans".
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.
authors.affiliation: 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. mpersico@unisa.it.
authors.forename: Marcello
authors.identifier: http://orcid.org/0000-0002-1399-6498
authors.initials: M
authors.lastname: Persico
authors.affiliation: 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.
authors.forename: Mario
authors.initials: M
authors.lastname: Masarone
authors.affiliation: Vascular Physiopathology Unit IRCCS, INM Neuromed, Pozzilli, IS, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Damato
authors.affiliation: Vascular Physiopathology Unit IRCCS, INM Neuromed, Pozzilli, IS, Italy.
authors.forename: Mariateresa
authors.initials: M
authors.lastname: Ambrosio
authors.affiliation: Hepato-Gastroenterology Division, University of Campania "L. Vanvitelli", Naples, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Federico
authors.affiliation: Internal Medicine and Hepatology Department, University of Campania "L. Vanvitelli", Naples, Italy.
authors.forename: Valerio
authors.initials: V
authors.lastname: Rosato
authors.affiliation: 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.
authors.forename: Tommaso
authors.initials: T
authors.lastname: Bucci
authors.affiliation: Vascular Physiopathology Unit IRCCS, INM Neuromed, Pozzilli, IS, Italy.
authors.forename: Albino
authors.initials: A
authors.lastname: Carrizzo
authors.affiliation: Department of Medicine and Surgery, University of Salerno, Salerno, Italy.
authors.forename: Carmine
authors.initials: C
authors.lastname: Vecchione
mesh_terms: D000328:Adult; D000818:Animals; D001011:Aorta / Q000378:metabolism; D001706:Biopsy; D001792:Blood Platelets / Q000378:metabolism; D016022:Case-Control Studies; D005234:Fatty Liver / Q000473:pathology / Q000503:physiopathology; D005260:Female; D006801:Humans; D007333:Insulin Resistance; D008099:Liver / Q000098:blood supply* / Q000473:pathology; D008297:Male; D051379:Mice; D008875:Middle Aged; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D065626:Non-alcoholic Fatty Liver Disease / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology*; D010766:Phosphorylation; D011446:Prospective Studies; D014664:Vasodilation
chemical_list: C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III
keywords: Endothelial dysfunction; Insulin resistance; Metabolic syndrome; Non-alcoholic fatty liver disease