Abstract
Angiogenesis involves the activation of endothelial cells followed by capillary formation. Leptin, the protein product of the ob gene, can induce the angiogenic potential of endothelial cells. However, the underlying cellular mechanism still remains to be elicited. We firstly evaluated the in vitro effects of leptin on proliferation and angiogenic differentiation of endothelial cell line EA.hy926. Leptin was found to potently induced cell proliferation, expression of angiogenic gene, migration and tube formation. Then we investigated the roles of the Akt and Wnt signaling pathways in the aforementioned processes. It showed that Akt and Wnt signaling pathways could be activated by leptin, while inhibition of the Akt and Wnt signaling pathways by siRNAs effectively blocked the leptin-induced angiogenesis. Finally, we used electrospinning to fabricated leptin-immobilized linear poly(L-lactide-co-caprolactone) (PLCL)-leptin. The in vivo vessel formation of PLCL-leptin was evaluated using subcutaneous implants in Sprague-Dawley rats. The histological and immunofluorescence revealed that cell infiltration with PLCL-leptin was much more significant than that with the control PLCL group. More importantly, the number of laminin+ vessels and CD31+ cells in PLCL-leptin grafts was significantly higher than in control grafts. The study demonstrated that it is via Akt and Wnt signaling pathways that leptin promotes the proliferation and angiogenic differentiation of endothelial cells and the capacity of endogenous tissue regeneration makes the novel leptin-conjugated PLCL promising materials for grafts.
Highlights
Cardiovascular diseases produce serious health problems to the humans worldwide (Roth et al, 2015)
We methodically demonstrated the effects of leptin on the proliferation and angiogenesis processes of endothelial cells with a special light cast on the cellular mechanism underlying leptin-induced angiogenesis and the crosstalk between the Akt and Wnt signaling pathways in vitro
The expression patterns of related angiogenesis genes in endothelial cells cultured in different concentrations of leptin were analyzed using quantitative realtime polymerase chain reaction (PCR) and western blot
Summary
Cardiovascular diseases produce serious health problems to the humans worldwide (Roth et al, 2015). Artificial vascular grafts are with success utilize in clinical applications for large-diameter blood vessels, but fail attribute to the poor patency used as small- to medium-sized grafts (SMGs) (Zilla et al, 2007). Angiogenesis is a physiological process that includes the activation of endothelial cells followed by the development of new capillary vessels (Maragoudakis, 2000). Because of cost, biological half-life, uncertain side effect limited their clinical application (Epstein et al, 2001; Lee et al, 2003; Taraboletti and Giavazzi, 2004)
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