Critical Role of LSEC in Post-Hepatectomy Liver Regeneration and Failure

Liver sinusoids are lined by liver sinusoidal endothelial cells (LSEC), which represent approximately 15 to 20% of the liver cells, but only 3% of the total liver volume. LSEC have unique functions, such as fluid filtration, blood vessel tone modulation, blood clotting, inflammatory cell recruitment, and metabolite and hormone trafficking. Different subtypes of liver endothelial cells are also known to control liver zonation and hepatocyte function. Here, we have reviewed the origin of LSEC, the different subtypes identified in the liver, as well as their renewal during homeostasis. The liver has the exceptional ability to regenerate from small remnants. The past decades have seen increasing awareness in the role of non-parenchymal cells in liver regeneration despite not being the most represented population. While a lot of knowledge has emerged, clarification is needed regarding the role of LSEC in sensing shear stress and on their participation in the inductive phase of regeneration by priming the hepatocytes and delivering mitogenic factors. It is also unclear if bone marrow-derived LSEC participate in the proliferative phase of liver regeneration. Similarly, data are scarce as to LSEC having a role in the termination phase of the regeneration process. Here, we review what is known about the interaction between LSEC and other liver cells during the different phases of liver regeneration. We next explain extended hepatectomy and small liver transplantation, which lead to “small for size syndrome” (SFSS), a lethal liver failure. SFSS is linked to endothelial denudation, necrosis, and lobular disturbance. Using the knowledge learned from partial hepatectomy studies on LSEC, we expose several techniques that are, or could be, used to avoid the “small for size syndrome” after extended hepatectomy or small liver transplantation.

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Role of Amphiregulin in Suppressed Liver Regeneration after Small-For-Size Liver Transplantation in Mice

Transplantation Journal ◽

10.1097/00007890-201211271-00694 ◽

2012 ◽

Vol 94 (10S) ◽

pp. 376

Author(s):

Q. Liu ◽

H. Rehman ◽

Y. Krishnasamy ◽

K. Haque ◽

R. G. Schnellmann ◽

...

Keyword(s):

Liver Transplantation ◽

Liver Regeneration ◽

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Role of Amphiregulin in Suppressed Liver Regeneration after Small-For-Size Liver Transplantation in Mice

Transplantation Journal ◽

10.1097/00007890-201211271-01267 ◽

2012 ◽

Vol 94 (10S) ◽

pp. 649

Author(s):

Q. Liu ◽

H. Rehman ◽

Y. Krishnasamy ◽

K. Haque ◽

R. G. Schnellmann ◽

...

Keyword(s):

Liver Transplantation ◽

Liver Regeneration ◽

Small For Size

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Shear stress augments mitochondrial ATP generation that triggers ATP release and Ca2+ signaling in vascular endothelial cells

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00204.2018 ◽

2018 ◽

Vol 315 (5) ◽

pp. H1477-H1485 ◽

Cited By ~ 15

Author(s):

Kimiko Yamamoto ◽

Hiromi Imamura ◽

Joji Ando

Keyword(s):

Endothelial Cells ◽

Shear Stress ◽

Vascular Endothelial Cells ◽

Critical Role ◽

Atp Release ◽

Vascular Endothelial ◽

The Novel ◽

Caveolin 1 ◽

Atp Generation

Vascular endothelial cells (ECs) sense and transduce hemodynamic shear stress into intracellular biochemical signals, and Ca2+ signaling plays a critical role in this mechanotransduction, i.e., ECs release ATP in the caveolae in response to shear stress and, in turn, the released ATP activates P2 purinoceptors, which results in an influx into the cells of extracellular Ca2+. However, the mechanism by which the shear stress evokes ATP release remains unclear. Here, we demonstrated that cellular mitochondria play a critical role in this process. Cultured human pulmonary artery ECs were exposed to controlled levels of shear stress in a flow-loading device, and changes in the mitochondrial ATP levels were examined by real-time imaging using a fluorescence resonance energy transfer-based ATP biosensor. Immediately upon exposure of the cells to flow, mitochondrial ATP levels increased, which was both reversible and dependent on the intensity of shear stress. Inhibitors of the mitochondrial electron transport chain and ATP synthase as well as knockdown of caveolin-1, a major structural protein of the caveolae, abolished the shear stress-induced mitochondrial ATP generation, resulting in the loss of ATP release and influx of Ca2+ into the cells. These results suggest the novel role of mitochondria in transducing shear stress into ATP generation: ATP generation leads to ATP release in the caveolae, triggering purinergic Ca2+ signaling. Thus, exposure of ECs to shear stress seems to activate mitochondrial ATP generation through caveola- or caveolin-1-mediated mechanisms. NEW & NOTEWORTHY The mechanism of how vascular endothelial cells sense shear stress generated by blood flow and transduce it into functional responses remains unclear. Real-time imaging of mitochondrial ATP demonstrated the novel role of endothelial mitochondria as mechanosignaling organelles that are able to transduce shear stress into ATP generation, triggering ATP release and purinoceptor-mediated Ca2+ signaling within the cells.

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LncRNA LUADT1 sponges miR-195 to prevent cardiac endothelial cell apoptosis in sepsis

Molecular Medicine ◽

10.1186/s10020-020-00228-5 ◽

2020 ◽

Vol 26 (1) ◽

Author(s):

Zhimin Zhang ◽

Mingzhu Lv ◽

Xiang Wang ◽

Zheng Zhao ◽

Daolong Jiang ◽

...

Keyword(s):

Endothelial Cells ◽

Endothelial Cell ◽

Cell Apoptosis ◽

Critical Role ◽

Potential Interaction ◽

Luciferase Reporter ◽

Endothelial Cell Apoptosis ◽

Luciferase Activity Assay ◽

Apoptosis Related Protein

Abstract Background The oncogenic role of the newly identified lncRNA LUADT1 has been revealed in lung adenocarcinoma. It was reported that LUADT1 plays a critical role in multiple human diseases. This study was carried out to investigate the role of LUADT1 in sepsis. Methods Sixty patients with sepsis and sixty healthy volunteers were recruited for this study. Plasma samples were collected from all participants. Human primary coronary artery endothelial cells were also used in this study. The expression of Pim-1, miR-195 and LUADT1 were detected by RT-qPCR. The interaction between miR-195 and LUADT1 was determined by overexpression experiments and luciferase activity assay. Cell apoptosis was detected by flow cytometry. The expression of apoptosis-related protein was detected by Western blotting. Results Bioinformatics analysis revealed the potential interaction between LUADT1 and miR-195, which was confirmed by dual luciferase reporter assay. LUADT1 was downregulated in patients with sepsis. Moreover, LPS treatment downregulated the expression of LUADT1 in primary cardiac endothelial cells. Overexpression of LUADT1 and miR-195 did not affect the expression of each other in primary cardiac endothelial cells. Interestingly, overexpression of LUADT1 was found to upregulate the expression of Pim-1, a target of miR-195. In addition, it was found that overexpression of LUADT1 and Pim-1 reduced the enhancement effects of miR-195 on LPS-induced cardiac endothelial cell apoptosis. Conclusion In summary, LUADT1 may protect cardiac endothelial cells against apoptosis in sepsis by regulating the miR-195/Pim-1 axis.

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Critical Role of NADPH Oxidase-derived Reactive Oxygen Species in Generating Ca2+ Oscillations in Human Aortic Endothelial Cells Stimulated by Histamine

Journal of Biological Chemistry ◽

10.1074/jbc.m201550200 ◽

2002 ◽

Vol 277 (36) ◽

pp. 32546-32551 ◽

Cited By ~ 52

Author(s):

Qinghua Hu ◽

Zu-Xi Yu ◽

Victor J. Ferrans ◽

Kazuyo Takeda ◽

Kaikobad Irani ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Endothelial Cells ◽

Nadph Oxidase ◽

Critical Role ◽

Reactive Oxygen ◽

Oxygen Species ◽

Aortic Endothelial Cells ◽

Human Aortic Endothelial Cells ◽

Aortic Endothelial

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Augmenter of liver regeneration promotes hepatic regeneration depending on the integrity of Kupffer cell in rat small-for-size liver transplantation

Journal of Surgical Research ◽

10.1016/j.jss.2013.02.033 ◽

2013 ◽

Vol 183 (2) ◽

pp. 922-928 ◽

Cited By ~ 12

Author(s):

Kang Yang ◽

Chengyou Du ◽

Yong Cheng ◽

Yue Li ◽

JianPing Gong ◽

...

Keyword(s):

Liver Transplantation ◽

Liver Regeneration ◽

Kupffer Cell ◽

Hepatic Regeneration ◽

Augmenter Of Liver Regeneration ◽

Small For Size

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Eicosanoid regulation of angiogenesis: role of endothelial arachidonate 12-lipoxygenase

Blood ◽

10.1182/blood.v95.7.2304.007k23_2304_2311 ◽

2000 ◽

Vol 95 (7) ◽

pp. 2304-2311

Author(s):

Daotai Nie ◽

Keqin Tang ◽

Clement Diglio ◽

Kenneth V. Honn

Keyword(s):

Endothelial Cells ◽

Cell Migration ◽

Endothelial Cell ◽

Growth Factor ◽

Cell Line ◽

Critical Role ◽

Endothelial Cell Migration ◽

Vascular Endothelial ◽

12 Lipoxygenase

Angiogenesis, the formation of new capillaries from preexisting blood vessels, is a multistep, highly orchestrated process involving vessel sprouting, endothelial cell migration, proliferation, tube differentiation, and survival. Eicosanoids, arachidonic acid (AA)-derived metabolites, have potent biologic activities on vascular endothelial cells. Endothelial cells can synthesize various eicosanoids, including the 12-lipoxygenase (LOX) product 12(S)-hydroxyeicosatetraenoic acid (HETE). Here we demonstrate that endogenous 12-LOX is involved in endothelial cell angiogenic responses. First, the 12-LOX inhibitor, N-benzyl-N-hydroxy-5-phenylpentanamide (BHPP), reduced endothelial cell proliferation stimulated either by basic fibroblast growth factor (bFGF) or by vascular endothelial growth factor (VEGF). Second, 12-LOX inhibitors blocked VEGF-induced endothelial cell migration, and this blockage could be partially reversed by the addition of 12(S)-HETE. Third, pretreatment of an angiogenic endothelial cell line, RV-ECT, with BHPP significantly inhibited the formation of tubelike/cordlike structures within Matrigel. Fourth, overexpression of 12-LOX in the CD4 endothelial cell line significantly stimulated cell migration and tube differentiation. In agreement with the critical role of 12-LOX in endothelial cell angiogenic responses in vitro, the 12-LOX inhibitor BHPP significantly reduced bFGF-induced angiogenesis in vivo using a Matrigel implantation bioassay. These findings demonstrate that AA metabolism in endothelial cells, especially the 12-LOX pathway, plays a critical role in angiogenesis.

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