Increased Circulating Angiopoietin-Like Protein 8 Levels Are Associated with Thoracic Aortic Dissection and Higher Inflammatory Conditions

Yang, Yunyun; Jiao, Xiaolu; Li, Linyi; Hu, Chaowei; Zhang, Xiaoping; Pan, Lili; Yu, Huahui; Li, Juan; Chen, Dong; Du, Jie; Qin, Yanwen

doi:10.1007/s10557-019-06924-7

Cited by 31 publications

(28 citation statements)

References 48 publications

(45 reference statements)

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“…Notably, compared with that in non-AAD tissues, the fraction of monocytes and macrophages in AAD tissues was significantly increased in both the training set and validation set, which indicates that the results were reliable. Analysis of the correlations between hub genes and CD14 and CD68, cell markers of monocytes and macrophages, in both the training set and validation set was performed to investigate the mechanism of immunoinflammatory responses in the development of AAD (7,21,24).…”

Section: Discussionmentioning

confidence: 99%

Analysis of Hub Genes and the Mechanism of Immune Infiltration in Stanford Type a Aortic Dissection

Gao

Sun

Liu

et al. 2021

Front. Cardiovasc. Med.

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Background: Stanford type A aortic dissection (AAD) is a catastrophic disease. An immune infiltrate has been found within the aortic wall of dissected aortic specimens. The recall and activation of macrophages are key events in the early phases of AAD. Herein, the immune filtration profile of AAD was uncovered.Methods: Gene expression data from the GSE52093, GSE98770 and GSE153434 datasets were downloaded from the Gene Expression Omnibus (GEO). The differentially expressed genes (DEGs) of each dataset were calculated and then integrated. A protein-protein interaction (PPI) network was established with the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), and the hub genes were identified in Cytoscape. Furthermore, gene ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of hub genes were performed. Finally, we set GSE52093 and GSE98770 as the training set and GSE153434 as the validation set to assess immune infiltration in AAD using CIBERSORTx and analyzed the correlations between immune cells and hub genes in both the training and validation sets.Results: Sixty-one integrated DEGs were identified. The top 10 hub genes were selected from the PPI network, and 140 biological process (BP) terms and 12 pathways were enriched among the top 10 hub genes. The proportions of monocytes and macrophages were significantly higher in AAD tissues than in normal tissues. Notably, this result was consistent in the training set and the validation set. In addition, we found that among the hub genes, CA9, CXCL5, GDF15, VEGFA, CCL20, HMOX1, and SPP1 were positively correlated with CD14, a cell marker of monocytes, while CA9, CXCL5, GDF15, and VEGFA were positively correlated with CD68, a cell marker of macrophages in the training set. Finally, according to the results of the GO and KEGG analysis of hub genes, we found that the monocyte/macrophage-related genes were involved in immune-inflammatory responses through degradation of the extracellular matrix, endothelial cell apoptosis, hypoxia and the interaction of cytokines and chemokines.Conclusion: The monocyte-macrophage system plays a major role in immune-inflammatory responses in the development of AAD. Several hub genes are involved in this process via diverse mechanisms.

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Section: Discussionmentioning

confidence: 99%

Analysis of Hub Genes and the Mechanism of Immune Infiltration in Stanford Type a Aortic Dissection

Gao

Sun

Liu

et al. 2021

Front. Cardiovasc. Med.

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“…The ANGPTL family has also been reported to play important roles in angiogenesis, inflammation, and cancer and has recently been implicated in the regulation of stem cell activity [12,[49][50][51][52]. The circulating levels of ANGPTL8/betatrophin are increased under high levels of inflammation [53]. Inflammatory stimuli have been reported to induce the expression of ANGPTL8/ betatrophin, which negatively regulates the activation of one of the most important central regulators of inflammation, nuclear factor-κB (NF-κB), to regulate inflammation [54].…”

Section: Discussionmentioning

confidence: 99%

Analysis of the Expression and Prognostic Potential of a Novel Metabolic Regulator ANGPTL8/Betatrophin in Human Cancers

Tian

Shi

et al. 2021

Pathol. Oncol. Res.

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The angiopoietin-like protein (ANGPTL) family members, except for the novel atypical member ANGPTL8/betatrophin, have been reported to participate in angiogenesis, inflammation and cancer. ANGPTL8/betatrophin is a metabolic regulator that is involved in lipid metabolism and glucose homeostasis. However, little is known about the expression and prognostic value of ANGPTL8/betatrophin in human cancers. In this study, we first conducted detailed analyses of ANGPTL8/betatrophin expression in cancer/normal samples via the Human Protein Atlas (HPA), Gene Expression Profiling Interactive Analysis (GEPIA), DriverDBv3, ENCORI and UALCAN databases. ANGPTL8/betatrophin showed high tissue specificity (enriched in the liver) and cell-type specificity (enriched in HepG2 and MCF7 cell lines). More than one databases demonstrated that the gene expression of ANGPTL8/betatrophin was significantly lower in cholangiocarcinoma (CHOL), breast invasive carcinoma (BRCA), lung adenocarcinoma (LUAD), lung squamous cell carcinoma (LUSC), uterine corpus endometrial carcinoma (UCEC), and significantly higher in kidney renal clear cell carcinoma (KIRC) compared with that in normal samples. However, the protein expression of ANGPTL8/betatrophin displayed opposite results in clear cell renal cell carcinoma (ccRCC)/KIRC. Based on the expression profiles, the prognostic value was evaluated with the GEPIA, DriverDBv3, Kaplan Meier plotter and ENCORI databases. Two or more databases demonstrated that ANGPTL8/betatrophin significantly affected the survival of KIRC, uterine corpus endometrial carcinoma (UCEC), pheochromocytoma and paraganglioma (PCPG) and sarcoma (SARC); patients with PCPG and SARC may benifit from high ANGPTL8/betatrophin expression while high ANGPTL8/betatrophin expression was associated with poor prognosis in KIRC and UCEC. Functional analyses with the GeneMANIA, Metascape and STRING databases suggested that ANGPTL8/betatrophin was mainly involved in lipid homeostasis, especially triglyceride and cholesterol metabolism; glucose homeostasis, especially insulin resistance; AMPK signaling pathway; PI3K/Akt signaling pathway; PPAR signaling pathway; mTOR signaling pathway; HIF-1 signaling pathway; autophagy; regulation of inflammatory response. ANGPTL8/betatrophin may be a promising prognostic biomarker and therapeutic target, thus providing evidence to support further exploration of its role in defined human cancers.

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“…Therefore, we speculate that ANGPTL8 may promote the development of DN through inflammatory mechanisms. ANGPTL8 has been proven to positively correlate with hs-CRP, leading to higher inflammatory conditions in thoracic aortic dissection ( 37 ). Sinha SK et al ( 38 ) reported that elevated serum levels of hs-CRP were associated with, and possibly influenced the development of DN, even for those without DM at baseline.…”

Section: Discussionmentioning

confidence: 99%

Association of ANGPTL8 and Resistin With Diabetic Nephropathy in Type 2 Diabetes Mellitus

Fan

Peng

et al. 2021

Front. Endocrinol.

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BackgroundPrevious studies showed altered angiopoietin-like protein-8 (ANGPTL-8) and resistin circulating levels in type 2 diabetes mellitus (T2DM). Whether or not the alteration in ANGPTL-8 and resistin level can be a predictive maker for increased diabetic nephropathy risk remains unclear.AimTo Investigate the possible association of ANGPTL-8 and resistin with DN, and whether this association is affected by NAFLD status.MethodsA total of 278 T2DM patients were enrolled. Serum levels of ANGPTL8, resistin, BMI, blood pressure, duration of diabetes, glycosylated hemoglobin (HbA1c), fasting blood glucose (FPG), hypersensitive C-reactive protein (hs-CRP), lipid profile, liver, and kidney function tests were assessed. The relationship between DN with ANGPTL8 and resistin was analyzed in the unadjusted and multiple-adjusted regression models.ResultsSerum levels of ANGPTL8 and resistin were significantly higher in DN compared with T2DM subjects without DN (respectively; P <0.001), especially in non-NAFLD populations. ANGPTL8 and resistin showed positive correlation with hs-CRP (respectively; P<0.01), and negative correlation with estimated GFR (eGFR) (respectively; P=<0.001) but no significant correlation to HOMA-IR(respectively; P>0.05). Analysis showed ANGPTL8 levels were positively associated with resistin but only in T2DM patients with DN(r=0.1867; P<0.05), and this significant correlation disappeared in T2DM patients without DN. After adjusting for confounding factors, both ANGPTL8(OR=2.095, 95%CI 1.253-3.502 P=0.005) and resistin (OR=2.499, 95%CI 1.484-4.208 P=0.001) were risk factors for DN. Data in non-NAFLD population increased the relationship between ANGPTL8 (OR=2.713, 95% CI 1.494-4.926 P=0.001), resistin (OR=4.248, 95% CI 2.260-7.987 P<0.001)and DN. The area under the curve (AUC) on receiver operating characteristic (ROC) analysis of the combination of ANGPTL8 and resistin was 0.703, and the specificity was 70.4%. These data were also increased in non-NAFLD population, as the AUC (95%CI) was 0.756, and the specificity was 91.2%.ConclusionThis study highlights a close association between ANGPTL8, resistin and DN, especially in non-NAFLD populations. These results suggest that ANGPTL-8 and resistin may be risk predictors of DN.

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Increased Circulating Angiopoietin-Like Protein 8 Levels Are Associated with Thoracic Aortic Dissection and Higher Inflammatory Conditions

Cited by 31 publications

References 48 publications

Analysis of Hub Genes and the Mechanism of Immune Infiltration in Stanford Type a Aortic Dissection

Analysis of Hub Genes and the Mechanism of Immune Infiltration in Stanford Type a Aortic Dissection

Analysis of the Expression and Prognostic Potential of a Novel Metabolic Regulator ANGPTL8/Betatrophin in Human Cancers

Association of ANGPTL8 and Resistin With Diabetic Nephropathy in Type 2 Diabetes Mellitus

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