Nitric oxide in liver diseases

Abstract

Nitric oxide (NO) and its derivatives play important roles in the physiology and pathophysiology of the liver. Despite its diverse and complicated roles, certain patterns of the effect of NO on the pathogenesis and progression of liver diseases are observed. In general, NO derived from endothelial NO synthase (eNOS) in liver sinusoidal endothelial cells (LSECs) is protective against disease development, while inducible NOS (iNOS)-derived NO contributes to pathological processes. This review addresses the roles of NO in the development of various liver diseases with a focus on recently published articles. We present here two recent advances in understanding NO-mediated signaling, nitrated fatty acids and S-guanylation, and conclude with suggestions on future directions of NO-related studies on the liver.

The NOX1 isoform of NADPH oxidase is involved in dysfunction of liver sinusoids in nonalcoholic fatty liver disease

“…This is similar to our previous findings obtained in the an-giotensin II-infused hypertension model, in which ROS derived from NOX1 perturbed endothelium-dependent relaxation of aortic strips, leading to the development of systemic hypertension [12]. The dysfunction of LSECs is known to augment intrahepatic resistance to impair microcirculation in the liver [18,26]. In fact, increased intrahepatic resistance has been demonstrated in an isolated-perfused rat liver obtained from a cafeteria diet-fed model of NAFLD [27], a methionine-choline-deficient model of NASH [28], and from a model of LPS-induced endotoxemia [29].…”

Changes in blood microbiota profiles associated with liver fibrosis in obese patients: A pilot analysis

“…On the other hand, the proportion of genes from other pathways, such as nitrogenase of the Nif family, is significantly increased in fibrosis. This observation is interesting given the observed link between LF and the metabolism of nitrogen compounds such as nitric oxide …”

Effects of aging on liver microcirculatory function and sinusoidal phenotype

“…Further analysis revealed a global deregulation in the hepatic endothelial phenotype in aging as demonstrated by significant decrease in key vasodilatory pathways, including nitric oxide and heme oxygenase, increment in intracellular inflammation and oxidative stress, and reduction in the expression of functional and angiocrine markers such as stabilin‐2, CD32b (Xie et al, 2013), and VEGFR2 (Carpenter et al, 2005). Reduction in intrahepatic nitric oxide availability is of relevance considering its importance modulating the vascular tone (Gracia‐Sancho, Maeso‐Diaz, Fernandez‐Iglesias, Navarro‐Zornoza, & Bosch, 2015; Hori, Wiest, & Groszmann, 1998), exerting anti‐inflammatory effects (Iwakiri & Kim, 2015), and maintaining neighboring cells phenotype (Marrone et al, 2016; Xie et al, 2013). Reduced nitric oxide bioavailability might, at least in part, derive from diminished eNOS activity, which may be due to reduced VEGF‐p‐eNOS pathway (Kroll & Waltenberger, 1998), and from increased scavenging due to elevated oxidative stress (Gracia‐Sancho et al, 2008).…”