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. 2017 Mar 7;17(1):35.
doi: 10.1186/s12876-017-0592-y.

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

Marcello Persico  1 , Mario Masarone  2 , Antonio Damato  3 , Mariateresa Ambrosio  3 , Alessandro Federico  4 , Valerio Rosato  5 , Tommaso Bucci  2 , Albino Carrizzo  3 , Carmine Vecchione  6
Affiliations

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

Marcello Persico et al. BMC Gastroenterol. .

Erratum in

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.

Keywords: Endothelial dysfunction; Insulin resistance; Metabolic syndrome; Non-alcoholic fatty liver disease.

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Figures

Fig. 1
Fig. 1
Dose-response curves of phenylephrine-precontracted aorta rings to supernatants derived from stimulated platelets isolated from NASH, Steatosis patients (“NAFL”) or Control subjects. Steatosis vs. controls:*, p < 0.05; **, p < 0.001; NASH vs. Steatosis: #, p < 0.05; ##, p < 0,001; NASH vs. controls: ‡, p < 0.05
Fig. 2
Fig. 2
Representative immunoblotting of eNOS phosphorylation at serine residue 1177 and Akt in threonine 308 in platelets and relative densitometric analysis for p-eNOS (left panel), p-Akt (central panel) and eNOS (right panel)
Fig. 3
Fig. 3
Immunohistochemistry of p-eNOS in the liver. Immunohistochemistry was performed on liver from three experimental condition: CTRL [control], NASH and Steatosis (“NAFL”). Insets represent higher magnification micrographs of p-eNOS immunoreactivity
Fig. 4
Fig. 4
Flow-mediated dilation evaluation of patients and controls in our study population
See this image and copyright information in PMC

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References

    1. Chalasani N, Younossi Z, Lavine JE, Diehl AM, Brunt EM, Cusi K, Charlton M, Sanyal AJ. The diagnosis and management of non-alcoholic fatty liver disease: practice Guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association. Hepatology. 2012;55(6):2005–2023. doi: 10.1002/hep.25762. - DOI - PubMed
    1. Matteoni CA, Younossi ZM, Gramlich T, Boparai N, Liu YC, McCullough AJ. Nonalcoholic fatty liver disease: a spectrum of clinical and pathological severity. Gastroenterology. 1999;116(6):1413–1419. doi: 10.1016/S0016-5085(99)70506-8. - DOI - PubMed
    1. White DL, Kanwal F, El-Serag HB. Association between nonalcoholic fatty liver disease and risk for hepatocellular cancer, based on systematic review. Clin Gastroenterol Hepatol. 2012;10(12):1342–1359. doi: 10.1016/j.cgh.2012.10.001. - DOI - PMC - PubMed
    1. McCuskey RS, Ito Y, Robertson GR, McCuskey MK, Perry M, Farrell GC. Hepatic microvascular dysfunction during evolution of dietary steatohepatitis in mice. Hepatology. 2004;40(2):386–393. doi: 10.1002/hep.20302. - DOI - PubMed
    1. Seifalian AM, Chidambaram V, Rolles K, Davidson BR. In vivo demonstration of impaired microcirculation in steatotic human liver grafts. Liver Transpl Surg. 1998;4(1):71–77. doi: 10.1002/lt.500040110. - DOI - PubMed

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