Sinusoidal Obstruction Syndrome

Sinusoidal obstructive syndrome (SOS) is a fibrous occlusive disease of hepatic sinusoids or hepatic venules. Small hepatic blood vessel damage, especially hepatic sinusoidal endothelial cell damage, is its main feature. Based on etiology, SOS is mainly classified into pyrrolidine alkaloids-related SOS, hematopoietic stem cell transplantation-related SOS, and SOS of unknown etiology. In recent years, the incidence of SOS has been increasing. However, due to the complexity of the etiology, the lack of specificity in clinical manifestations, the difficulty of early diagnosis, and the limited treatment options, it often leads to poor treatment effects and even death. This chapter aims to analyze and organize the pathogenesis, pathological characteristics, diagnosis, treatment, and prognosis of different types of SOS, to provide certain references for the prevention and treatment of the disease.

SIRT1 ameliorates premature senescence-induced defenestration in hepatic sinusoidal endothelial cell

Premature senescence, linked to progerin, involves in endothelial dysfunction and liver diseases. Activating sirtuin 1 (SIRT1) ameliorates liver fibrosis. However, the potential mechanisms of premature senescence in defenestration in hepatic sinusoidal endothelial cells (HSECs) and how SIRT1 affects fenestrae remains elusive. Our study showed that in vivo, premature senescence occurred, with decrease of SIRT1, during CCl4-induced defenestration in HSECs and liver fibrogenesis; whereas overexpressing SIRT1 with adenovirus vector lessened progerin-associated premature senescence to relieve CCl4-induced defenestration and liver fibrosis. In vitro, fenestrae in HSECs disappeared, with progerin-associated premature senescence; these effects aggravated by H2O2-induced oxidative damage. Nevertheless, knockdown of NOX2 or overexpression of SIRT1 with adenovirus vector reduced progerin-associated premature senescence to maintain fenestrae through deacetylating p53. Furthermore, more Ac p53 K381 and progerin co-localized with accumulation of actin filament (F-actin) in the nuclear envelope of H2O2-treated HSECs; in contrast, these effects were rescued by overexpressing SIRT1. In conclusion, NOX2-dependent oxidative damage aggravates defenestration in HSECs via progerin-associated premature senescence; SIRT1-mediated deacetylation of p53 maintains fenestrae and attenuates liver fibrogenesis through inhibiting premature senescence.