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Nanosilicates Promote Angiogenesis Through Activation of ROS-Mediated WNT/β-Catenin Pathway

ABSTRACT: Scaffold vascularization plays a pivotal role in the wound healing process, facilitating the recruitment of endogenous progenitor cells and delivering crucial signaling molecules that promote cellular invasion, angiogenesis, and neo-tissue formation. In this study, we introduce nanosilicates as pro-angiogenic biomaterials that can prime endogenous cells to expedite angiogenesis and graft vascularization in vivo. Characterized by their mineral-based two-dimensional (2D) structure and extensive surface area, nanosilicates are efficiently internalized by endothelial cells, leading to augmented cellular migration and the formation of tubular structures. Through whole transcriptome sequencing, we elucidated that nanosilicates activate the canonical Wnt pathway through hypoxia-induced ROS production. In vivo investigations further corroborate the pro-angiogenic efficacy of nanosilicates-loaded biomaterials. This study posits nanosilicates as a potential pro-angiogenic adjunct in the design of biomaterials for in situ tissue regeneration.

ORGANISM(S): Homo sapiens

PROVIDER: GSE270943 | GEO | 2025/06/20

REPOSITORIES: GEO

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Project description:Disordered angiogenesis is implicated in the pulmonary vascular remodeling secondary to congenital heart disease (CHD). However, the underlying genes are not well delineated. We have previously shown that an ovine model of CHD with increased pulmonary blood flow (PBF, Shunt) has an M-bM-^@M-^\angiogenesis burstM-bM-^@M-^] between 1-4 weeks of age. Thus, we hypothesized that the increased pulmonary blood flow elicited a pro-angiogenic gene expression profile prior to the onset of vessel growth. To test this we utilized microarray analysis to identify genes that could be responsible for the angiogenic response. Total RNA was isolated from the lungs of Shunt and Control lambs at 3 days of age and hybridized to Affymetrix GeneChips for microarray analyses (n=8 for each group). A total of 89 angiogenesis-related genes were found to be up-regulated and 26 angiogenesis-related genes down-regulated in Shunt lungs compared to control (cutting at 1.2 fold difference, P<0.05). We then confirmed the up-regulation of pro-angiogenic genes: FGF2, Angiopoietin2 (Angpt2), and Birc5 at both mRNA and protein levels and the up-regulation of ccl2 at mRNA level in the 3-day shunt lungs. Further, we found that pulmonary arterial endothelial cells (PAEC) isolated from juvenile lambs exhibited increased expression of FGF2, Angpt2, Birc5, and ccl2 as well as enhanced angiogenesis when exposed to elevated shear stress (35 dyn/cm2) compared to cells exposed to more physiological level shear stress (20 dyn/cm2). Finally, we demonstrated that blocking FGF2, Angpt2, or Birc 5 signaling, using neutralizing antibodies, significantly decreased the angiogenic response induced by shear stress. In conclusion, we have identified a pro-angiogenic gene expression profile in a lamb model of CHD with increased PBF that precedes the onset of pulmonary vascular remodeling. Further, our data indicate that FGF2, Angiopoietin2, Birc5, and ccl2 may play important roles in the angiogenic response. Total RNA was isolated from the lungs of Shunt and Control lambs at 3 days of age and hybridized to Affymetrix GeneChips for microarray analyses. Eight chips were employed for both control and shunt groups.

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Nanosilicates Promote Angiogenesis Through Activation of ROS-Mediated WNT/β-Catenin Pathway

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