Tie‐ing Up Angiogenesis to Treat Nonalcoholic Steatohepatitis

Davidson, Nicholas O.

doi:10.1002/hep.30318

Cited by 1 publication

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References 10 publications

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“…13 In the present study, Angiogenesis has been reported to play an essential role in the pathogenesis of NASH. 25,26 However, in the present study, Angptl4…”

Section: Discussioncontrasting

confidence: 58%

Angiopoietin‐like protein 4 deficiency augments liver fibrosis in liver diseases such as nonalcoholic steatohepatitis in mice through enhanced free cholesterol accumulation in hepatic stellate cells

Teratani

Tomita

Wada

et al. 2021

Hepatology Research

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Aim : We recently reported that lipoprotein lipase (LPL)-mediated free cholesterol (FC) accumulation in hepatic stellate cells (HSCs) augmented liver fibrosis in nonalcoholic steatohepatitis (NASH). The aim of the present study was to explore the role of angiopoietin-like protein 4 (Angptl4), an LPL inhibitor, in the pathogenesis of liver fibrosis in NASH.Methods: Angptl4-deficient or wild-type mice were used to investigate the role of Angptl4 in the pathogenesis of NASH induced by feeding a methionine-and cholinedeficient diet. We also examined the effect of Angptl4 on FC accumulation in HSCs, and the subsequent activation of HSCs, using Angptl4-deficient HSCs.Results: In the NASH model, Angptl4-deficient mice had significantly aggravated liver fibrosis and activated HSCs without enhancement of hepatocellular injury, liver inflammation, or liver angiogenesis. FC levels were significantly higher in HSCs from Angptl4-deficient mice than in those from wild-type mice. Treatment with Angptl4 reversed low-density lipoprotein-induced FC accumulation in HSCs through the inhibition of LPL. The Angptl4 deficiency-induced FC accumulation in HSCs suppressed HSC expression of the transforming growth factor-β (TGF-ß) pseudoreceptor, bone morphogenetic protein, and activin membrane-bound inhibitor, and sensitized HSCs to TGF-β-induced activation in vivo and in vitro.

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“…13 In the present study, Angiogenesis has been reported to play an essential role in the pathogenesis of NASH. 25,26 However, in the present study, Angptl4…”

Section: Discussioncontrasting

confidence: 58%