ANGPT2 blocking peptide

Background: Improving vascularization of engineered adipose tissue constructs is a major challenge in the field of plastic surgery. Although human adipose-derived stromal cells (hASCs) are known to release factors that stimulate new blood vessel formation, detailed information about the effects of adipogenic differentiation on the angiogenic potential of hASCs remains largely unknown. In the present study, we studied the expression and secretion of a large panel of angiogenic factors during hASC differentiation and evaluated the effects of hASC-conditioned medium (hASC-CM) on endothelial cells. Methods: hASCs were cultured on adipogenic medium or basal medium. Conditioned medium was collected, and cells were harvested following 0, 3, 7, 14, and 22 days of culture. The stage of adipogenic differentiation of hASC was assessed using Oil Red O staining, fatty acid binding protein-4 gene expression, and glycerol-3-phosphate dehydrogenase activity. Results: Gene expression of vascular endothelial growth factor ( VEGF), placental growth factor, angiopoietin-1 (ANGPT1), angiopoietin-2 (ANGPT2), and protein secretion of VEGF significantly increased during short-term adipogenic differentiation of hASCs. Moreover, conditioned medium from differentiated hASCs strongly enhanced endothelial cell numbers compared to conditioned medium from undifferentiated hASCs. Conclusion: In vitro adipogenic differentiation of hASCs improves their ability to support endothelial viable cell numbers and suggests that hASCs differentiated for a short period potentially improve angiogenic responses for in vivo implantation.

OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) is an obesity-associated disease, and in obesity adipokines are believed to be involved in the development of NAFLD. However, it is still not clear whether adipokines in the liver and/or adipose tissues can be related to the development of specific characteristics of NAFLD, such as steatosis and inflammation. We aimed to address this question by simultaneously examining the adipokine expression in three tissue types in obese individuals. METHODS: We enrolled 93 severely obese individuals with NAFLD, varying from simple steatosis to severe non-alcoholic steatohepatitis. Their expression of 48 adipokines in the liver, visceral and subcutaneous adipose tissue (SAT) was correlated to their phenotypic features of NAFLD. We further determined whether the correlations were tissue specific and/or independent of covariates, including age, sex, obesity, insulin resistance and type 2 diabetes (T2D). RESULTS: The expression of adipokines showed a liver-and adipose tissue-specific pattern. We identified that the expression of leptin, angiopoietin 2 (ANGPT2) and chemerin in visceral adipose tissue (VAT) was associated with different NAFLD features, including steatosis, ballooning, portal and lobular inflammation. In addition, the expression of tumor necrosis factor (TNF), plasminogen activator inhibitor type 1 (PAI-1), insulin-like growth factor 1 (somatomedin C) (IGF1) and chemokine (C-X-C motif) ligand 10 (CXCL10) in the liver tissue and the expression of interleukin 1 receptor antagonist (IL1RN) in both the liver and SAT were associated with NAFLD features. The correlations between ANGPT2 and CXCL10, and NAFLD features were dependent on insulin resistance and T2D, but for the other genes the correlation with at least one NAFLD feature remained significant after correcting for the covariates. CONCLUSIONS: Our results suggest that in obese individuals, VAT-derived leptin and chemerin, and hepatic expression of TNF, IGF1, IL1RN and PAI-1 are involved in the development of NAFLD features. Further, functional studies are warranted to establish a causal relationship.