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Effect of endostatin administration on epididymal white adipose tissue gene expression in female mice during the day.

ABSTRACT: Endostatin is an endogenous cleavage product of Collagen 18 type a 1, an extracellular matrix protein that has anti-angiogenic properties. Increasing evidence suggests that endostatin has metabolic benefits in obesity models independently from its anti-angiogenic effects. Furthermore, multiple reports have shown drastic reduction in weight gain with endostatin treatment with high fat diet, and cell -autonomous effects of endostatin on adipocytes. The pathways that regulate endostatin 's effects on adipocytes are elusive. We have determined that there is a sex- and time-dependent effect of endostatin on adipose tissue gene expression. Therefore, we treated female mice with endostatin, collected adipose tissue and performed Total RNA-seq on RNA extracted from the tissue.

ORGANISM(S): Mus musculus

PROVIDER: GSE305072 | GEO | 2026/04/08

REPOSITORIES: GEO

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Project description:Background and Aims: Intracranial atherosclerotic disease (ICAD) carries high recurrence rates despite intensive medical management. Prior studies suggest anti-angiogenic circulating profiles may contribute to treatment failure. This exploratory study evaluated associations between pro- and anti-angiogenic factors and stroke patterns in ICAD, specifically comparing hemodynamic (borderzone) versus embolic presentations. Methods: We conducted a cross-sectional analysis of 110 patients with severe ICAD (≥70% stenosis) from four U.S. centers (2019-2023). Five circulating factors were measured: VEGF, VEGF-165b, HGF (pro-angiogenic), and endostatin, angiostatin (anti-angiogenic). Stroke patterns were classified as hemodynamic (borderzone/watershed, n=28) or non-hemodynamic (embolic/perforator, n=82) based on MRI. A Random Forest classifier was developed to identify biomarker patterns associated with stroke type, with feature importance analysis to determine relative contributions. Results: The Random Forest model achieved 85% accuracy (AUC 0.87) in discriminating hemodynamic from non-hemodynamic strokes using 5-fold cross-validation. Feature importance analysis revealed anti-angiogenic factors as the strongest predictors: angiostatin (25.6% importance) and endostatin (21.5%), followed by pro-angiogenic factors VEGF (18.3%) and HGF (18.1%). Secondary analyses showed moderate associations with functional independence (AUC 0.71) but not cognitive scores. Exosomal microRNA pathway analysis revealed enrichment in pathways common to both neurovascular insufficiency and neurodegenerative processes, suggesting potential shared mechanisms between vascular and degenerative pathologies. Conclusions: This hypothesis-generating study identifies differential expression of angiogenic factors associated with hemodynamic versus embolic stroke patterns in ICAD. The predominance of anti-angiogenic factors in predicting hemodynamic strokes suggests impaired collateral formation may contribute to watershed ischemia. These preliminary associations warrant prospective validation to determine whether anti-angiogenic profiles could identify ICAD patients at risk for hemodynamic compromise.

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Effect of endostatin administration on epididymal white adipose tissue gene expression in female mice during the day.

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