Hepatic sinusoids versus central veins: Structures, markers, angiocrines, and roles in liver regeneration and homeostasis

Abstract

The blood circulates through the hepatic sinusoids delivering nutrients and oxygen to the liver parenchyma and drains into the hepatic central vein, yet the structures and phenotypes of these vessels are distinctively different. Sinusoidal endothelial cells are uniquely fenestrated, lack basal lamina and possess organelles involved in endocytosis, pinocytosis, degradation, synthesis and secretion. Hepatic central veins are nonfenestrated but are also active in synthesis and secretion. Endothelial cells of sinusoids and central veins secrete angiocrines that play respective roles in hepatic regeneration and metabolic homeostasis. The list of markers for identifying sinusoidal endothelial cells is long and their terminologies are complex. Further, their uses vary in different investigations and, in some instances, could be confusing. Central vein markers are fewer but more distinctive. Here we analyze and categorize the molecular pathways/modules associated with the sinusoid‐mediated liver regeneration in response to partial hepatectomy and chemical‐induced acute or chronic injury. Similarly, we highlight the findings that central vein‐derived angiocrines interact with Wnt/β‐catenin in perivenous hepatocytes to direct gene expression and maintain pericentral metabolic zonation. The proposal that perivenous hepatocytes behave as stem/progenitor cells to provoke hepatic homeostatic cell renewal is reevaluated and newer concepts of broad zonal distribution of hepatocyte proliferation in liver homeostasis and regeneration are updated. Thus, this review integrates the structures, biology and physiology of liver sinusoids and central veins in mediating hepatic regeneration and metabolic homeostasis.

Alcohol‐associated capillarization of sinusoids: A critique since the discovery by Schaffner and Popper in 1963

“…S, sinusoid; SD, space of Disse. (a) with permission of Wiley of endothelial cells and their immunocytochemical markers, see reviews by Wisse et al (1999) and Mak and Shin (2021).…”

“…Their sizes range from 50 to 300 nm in diameter, depending on the animal or human species derived from, age, and methods of visualization by microscopy. There are 3–20 fenestrations per μm 2 of the endothelial surface area, which cover as much as 20% of the cell surface (Braet & Wisse, 2002; Cogger et al, 2020; Fraser et al, 2012; Mak & Shin, 2021; Sorensen & Smedsrod, 2020; Wisse et al, 1999). The mean lifespan of mouse fenestrations is ~18 hr (Zapotoczny et al, 2019).…”

“…In rats, periportal fenestrations are larger in diameter and fewer in number whereas centrilobular fenestrations are smaller in diameter and greater in number, which was first observed and reported by Wisse et al (1983) and later in other studies (Kanaoka et al, 1988; Okanoue et al, 1999; Takashimizu et al, 1999). For fine structure of endothelial cells and their immunocytochemical markers, see reviews by Wisse et al (1999) and Mak and Shin (2021).…”

“…In these three aforementioned studies, the zonal origin of isolated LSECs was unknown, given the heterogeneity of endothelial cells across the liver lobule of rats and humans (Mak & Shin, 2021; Sorensen & Smedsrod, 2020; Strauss et al, 2017; Xie et al, 2010). Likewise, the viability, purity, and identity were not reported.…”

HIV DNA persists in hepatocytes in people with HIV-hepatitis B co-infection on antiretroviral therapy

“… 31 , 39 , 40 , 41 , 42 In studies of PWH on ART or non-human primates infected with either simian immunodeficiency virus (SIV) or a hybrid virus of SIV with an HIV envelope (SHIV) on ART who underwent autopsy, detection of HIV DNA or HIV RNA using quantitative (q)PCR or using in situ hybridisation has been reported in the liver at low but detectable levels in multiple studies, 43 , 44 , 45 , 46 however the location of infection within the liver has not been examined. Given that CD4+ T cells can be recruited to the liver during inflammation, 47 , 48 , 49 and that the liver is rich with blood in liver sinusoids, 50 detection of HIV DNA could potentially represent latently or productively infected CD4+ T cells and not true infection of liver cells.…”