AAMP Regulates Endothelial Cell Migration and Angiogenesis Through RhoA/Rho Kinase Signaling

Abstract

Angiogenesis is a complicated process including endothelial cell proliferation, migration and tube formation. AAMP plays a role in regulating cell migration of multiple cell types. The purpose of this study was to investigate whether AAMP regulates angiogenesis, and to clarify the role of AAMP in the VEGF-induced angiogenesis. We found that AAMP expressed in multiple cell types and mainly localized in cytoplasm and membrane in vascular endothelial cells. Using tube formation assay in vitro and aortic ring assay, siRNA-mediated knockdown and antibody blockade of AAMP impaired VEGF-induced endothelial cell tube formation and aortic ring angiogenic sprouting. Mechanistic studies showed that AAMP expression was significantly upregulated by VEGF in a concentration and time-dependent manner. Moreover, VEGF recruited AAMP to the cell membrane protrusions. AAMP regulates angiogenesis by mediating the spreading and migration of vascular endothelial cells. AAMP knock-down reduced VEGF-induced actin stress fibers and collagen gel contraction. Furthermore, we identified RhoA/Rho kinase signaling as an important factor that contributes to the action of AAMP in regulating endothelial cell migration and angiogenesis. Altogether, these data demonstrated the critical role of AAMP in angiogenesis and suggested blocking AAMP could serve as a potential therapeutic strategy for angiogenesis-related diseases.

Smart mechanosensing machineries enable migration of vascular smooth muscle cells in atherosclerosis‐relevant 3D matrices

“…We paid special attention to biomechanical regulation of cell migration in which actomyosin tension plays a critical role. Our previous studies have confirmed a leading role of actomyosin tension in regulating cell migration and angiogenesis, an essential step in generating atherosclerosis plaques (Qiu et al, ; Hu et al, ).…”

“…In 2D migration, actomyosin tension generates traction forces to translocate cell body and regulate assembly of focal adhesions through adhesions (Ridley et al, ). Our previous studies have implicated the important roles of cytoskeletal reorganization and focal adhesion assembly in cell adhesion and migration when the cells were overexpressing Id1 (Qiu et al, ), treated with oxLDLs (oxidized low‐density lipoprotein) in static conditions (Qiu et al, ; Qiu et al, ), or shear flow (Wei et al, ; Xie et al, ), placed on various matrices (Shen et al, ; Shen et al, ; Teng et al, ; Shen et al, ; Hu et al, ). We paid special attention to biomechanical regulation of cell migration in which actomyosin tension plays a critical role.…”

The Functional Implications of Endothelial Gap Junctions and Cellular Mechanics in Vascular Angiogenesis

“…In response to these pro-angiogenic and environmental factors, endothelial cells initiate angiogenic processes [3,4], which can be categorized as vascular sprouting [5], cell proliferation [6], cell migration [7], tube formation [8], and vascular stabilization [9]. Notably, during these angiogenic processes, endothelial cells dynamically alter cell mechanics, and physiological components determined by cytoskeletal rearrangement [10], focal adhesion formation [11], and contractile force [12], have also been observed.…”

The Functional Implication for Endothelial Gap Junction and Cellular Mechanics in Vascular Angiogenesis

“…In the response to these pro-angiogenic factors and environments, vascular endothelial cells (ECs) initiate angiogenic process including vascular sprouting, cell proliferation, cell migration, tube formation, and vascular stabilization [3,4]. Notably, during these angiogenic process, ECs dynamically changes of cell mechanics that are mechanical and physiological characters determined by cytoskeletal rearrangement [5], focal adhesion formation [6], and contractile force [7], have been also observed.…”