The Role of Angiopoietin-Like Proteins in Angiogenesis and Metabolism

Hato, Tai; Tabata, Mitsuhisa; Oike, Yuichi

doi:10.1016/j.tcm.2007.10.003

Cited by 302 publications

(304 citation statements)

References 84 publications

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“…1I) Table S1 and include up-regulation of genes previously shown to be induced by vGPCR expression (18). Of interest, this microarray analysis showed a robust up-regulation (13.14-fold) of the expression of angiopoietin like-4, a member of the family of Angiopoietin-like proteins (ANGPTLs) (19). Induction of vGPCR expression in both immortalized (HMEC1) or primary (HMVEC) human dermal microvascular endothelial cells correlated with a potent up-regulation of angptl4 mRNA levels, and translation and secretion of ANGPTL4 ( Fig.…”

Section: Vegf Is Not Sufficient For the Exudative Phenotype In Vgpcr mentioning

confidence: 75%

“…ANGPTL4 is a multifunctional factor with predominant expression in liver, adipose, and ischemic tissues, and is involved in the regulation of lipid metabolism and angiogenesis (19). Although its secretion has been shown to modulate the disposition of circulating triglycerides by inhibiting lipoprotein lipase, its role in vascular biology is less clear.…”

Section: Discussionmentioning

confidence: 99%

“…Compelling data suggests that vGPCR induces sarcomagenesis through the release of pro-and antiangiogenic cytokines, chemokines, and growth factors that ultimately promote the proangiogenic and proexudative response induced by this viral receptor (8,13). In this regard, ANGPTL proteins have been previously shown to regulate multiple aspects of endothelial cell function, including endothelial cell proliferation, migration, differentiation, and endothelial cell adhesion (19). However, conflicting data exists as to the pro-vs. antiangiogenic effects of ANGPTL4 (21)(22)(23)(24)(25)(26).…”

Section: Vegf Is Not Sufficient For the Exudative Phenotype In Vgpcr mentioning

confidence: 99%

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Viral G protein-coupled receptor up-regulates Angiopoietin-like 4 promoting angiogenesis and vascular permeability in Kaposi's sarcoma

Jham

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

109

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Kaposi's sarcoma (KS) is an enigmatic vascular tumor thought to be a consequence of dysregulated expression of the human herpesvirus-8 (HHV-8 or KSHV)-encoded G protein-coupled receptor (vGPCR). Indeed, transgenic animals expressing vGPCR manifest vascular tumors histologically identical to human KS, with expression of the viral receptor limited to a few cells, suggestive of a paracrine mechanism for vGPCR tumorigenesis. Both human and vGPCR experimental KS lesions are characterized by prominent angiogenesis and vascular permeability attributed to the release of angiogenic molecules, most notably vascular endothelial growth factor. However, the relative contribution of these paracrine mediators to the angiogenic and exudative phenotype of KS lesions remains unclear. Here we show that vGPCR up-regulation of Angiopoietin-like 4 (ANGPTL4) plays a prominent role in promoting the angiogenesis and vessel permeability observed in KS. Indeed, ANGPTL4 expression is a hallmark of vGPCR experimental and human KS lesions. Inhibition of ANGPTL4 effectively blocks vGPCR promotion of the angiogenic switch and vascular leakage in vitro and tumorigenesis in vivo. These observations suggest that ANGPTL4 is a previously unrecognized target for the treatment of patients with KS. As angiogenesis and increased vessel permeability are common themes in all solid tumors, these findings may have a broad impact on our understanding and treatment of cancer.

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Section: Vegf Is Not Sufficient For the Exudative Phenotype In Vgpcr mentioning

confidence: 75%

Section: Discussionmentioning

confidence: 99%

Section: Vegf Is Not Sufficient For the Exudative Phenotype In Vgpcr mentioning

confidence: 99%

See 1 more Smart Citation

Viral G protein-coupled receptor up-regulates Angiopoietin-like 4 promoting angiogenesis and vascular permeability in Kaposi's sarcoma

Jham

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

109

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“…Also, it has recently been shown that Angptl6 inhibits glucose production in rat hepatocytes by preventing expression of glucose-6-phosphatase, a key enzyme in gluconeogenesis [22]. Furthermore, Hato et al reported that diet-induced obese mice receiving Angptl6 showed increased adenosine monophosphate-activated protein kinase activity (which improves insulin signaling in skeletal muscle) and that, in C2C12 myoblasts, the addition of insulin after pretreatment with Angptl6 increased IRS-1 (insulin receptor substrate-1) phosphorylation, PI3-K (phosphatidylinositol 3-kinase) activity and glucose uptake, thereby resulting in enhanced insulin signaling [11].…”

Section: Discussionmentioning

confidence: 99%

“…The ANGPTL family has seven members (ANGPTL 1-7), which have been found in both humans and mice [11] (except for ANGPTL5, identified only in humans [12]). The ANGPTLs are secreted proteins that serve as endocrine signals in the peripheral tissues.…”

Section: Introductionmentioning

confidence: 99%

Association between angiopoietin-like 6 (ANGPTL6) gene polymorphisms and metabolic syndrome-related phenotypes in the French MONICA Study

Legry

Goumidi

Huyvaert

et al. 2009

Diabetes & Metabolism

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Angiopoietin‐like protein 4 and clinical outcomes in ischemic stroke patients

Zheng

Shen

Wang

et al. 2021

Ann Clin Transl Neurol

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Aims Angiopoietin‐like protein 4 (ANGPTL‐4) had been reported to be associated with the risk of ischemic stroke, but its prognostic value remained unclear. The aim of this study was to investigate the association between plasma ANGPTL‐4 concentrations and prognosis of ischemic stroke. Methods Baseline plasma ANGPTL‐4 concentrations were measured in 3379 acute ischemic stroke patients. The primary outcome was a combination of death or major disability (modified Rankin Scale score, ≥3) at 3 months after ischemic stroke. Results At 3 months after ischemic stroke, 850 (26.16%) participants experienced major disability or died (750 major disabilities and 100 deaths). After adjusting for important covariates, odds ratios for the highest tertile of plasma ANGPTL‐4 concentrations were 1.59 (1.22–2.06) for primary outcome, 1.53 (1.18–1.97) for major disability, and 2.03 (1.03–4.00) for death when compared with the lowest tertile of plasma ANGPTL‐4 concentrations. For 1‐SD increase in log‐ANGPTL‐4 concentrations (0.44 ng/mL), the adjusted odds ratios were 1.24 (1.11–1.38), 1.14 (1.03–1.27), and 1.72 (1.32–2.23), respectively. Adding ANGPTL‐4 to a model containing conventional risk factors improved risk prediction for composite outcome of death and major disability. Conclusion Higher plasma ANGPTL‐4 concentration was associated with poor prognosis in acute ischemic stroke patients, suggesting that ANGPTL‐4 might be a prognostic marker for ischemic stroke.

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The Role of Angiopoietin-Like Proteins in Angiogenesis and Metabolism

Cited by 302 publications

References 84 publications

Viral G protein-coupled receptor up-regulates Angiopoietin-like 4 promoting angiogenesis and vascular permeability in Kaposi's sarcoma

Viral G protein-coupled receptor up-regulates Angiopoietin-like 4 promoting angiogenesis and vascular permeability in Kaposi's sarcoma

Association between angiopoietin-like 6 (ANGPTL6) gene polymorphisms and metabolic syndrome-related phenotypes in the French MONICA Study

Angiopoietin‐like protein 4 and clinical outcomes in ischemic stroke patients

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