ArticleHepatology (Baltimore, Md.)2008
Nitric oxide promotes caspase-independent hepatic stellate cell apoptosis through the generation of reactive oxygen species.
Article in Hepatology (Baltimore, Md.), 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
57 citing papers in PubMed, 114 citations in OpenAlex.
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- The soluble guanylate cyclase stimulator riociguat reduces fibrogenesis and portal pressure in cirrhotic rats.Scientific reports · 2018Article
- Elevated mitochondrial activity distinguishes fibrogenic hepatic stellate cells and sensitizes for selective inhibition by mitotropic doxorubicin.Journal of cellular and molecular medicine · 2018Article
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Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
unlabelledHepatic stellate cells (HSCs) contribute to portal hypertension through multiple mechanisms that include collagen deposition, vasoconstriction, and regulation of sinusoidal structure. Under normal physiologic conditions, endothelial nitric oxide (NO) synthase-derived NO exerts paracrine effects on HSCs; however, in cirrhosis, NO generation is impaired in association with concomitant HSC activation and changes in sinusoidal structure, events that contribute significantly to the development of portal hypertension. These concepts, in combination with recent evidence that induction of HSC-selective apoptosis may represent a useful target for treatment of chronic liver disease, led us to examine if NO may further limit HSC function through apoptosis. Indeed, both NO donors and endothelial NO synthase overexpression promoted HSC apoptotic pathways. HSC death conferred by NO occurred through mitochondrial membrane depolarization and through a caspase-independent pathway. Furthermore, NO-induced apoptosis of HSC did not occur through the canonical pathways of soluble guanylate cyclase or protein nitration, but rather through the generation of superoxide and hydroxyl radical intermediates. Lastly, HSC isolated from rats after bile duct ligation were more susceptible to NO-induced apoptosis. These data indicate that NO promotes HSC apoptosis through a signaling mechanism that involves mitochondria, is mediated by reactive oxygen species, and occurs independent of caspase activation.
conclusionWe postulate that NO-dependent apoptosis of HSCs may maintain sinusoidal homeostasis, and may represent an additional beneficial effect of NO donors for therapy of portal hypertension.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.