Wall Shear Stress and Sphingosine‐1‐Phosphate Synergistically Activate Ca2+ Signaling via Piezo1 to Mediate Angiogenesis

• DOI: 10.1096/fasebj.2018.32.1_supplement.896.3
• Publication Date: 2021-06-21T16:44:18Z
• Authors: Hojin Kang; Manish Mittal; Ming Zhong; Yulia Komarova; Dolly Mehta; Asrar B. Malik
• Keywords: Piezo1; Sprouting angiogenesis; Mechanotransduction

The sensing of wall shear stress (WSS) by endothelial cells (ECs) mediates sprouting angiogenesis; however, the underlying signaling mechanisms remain unclear. Here we investigated synergism between WSS and angiogenic mediator Sphingosine‐1‐phosphate (S1P) in activation mechanosensitive ion channel protein Piezo1, expressed ECs. Studies were made EC monolayers exposed to 5 dyne/cm 2 , level approximating venular WSS, which angiogenesis 3D collagen matrix was assessed with without challenge S1P. or S1P alone induced little combined resulted robust suggesting that efficient requires both mechanical humoral stimuli. These responses inhibited suppression Piezo1 expression human murine as well vivo models. Specifically, studies mice conditionally deleted ECs ( iEC‐KO ) demonstrated requisite role S1P‐dependent mediating . functioned activating Ca 2+ gating function turn signaled calpain metalloproteinases, metalloproteinase‐2 (MMP2) membrane type 1‐matrix metalloproteinase (MT1‐MMP). synergizes induce influx via thereby activate activities MT1‐MMP, mediate angiogenesis. Support Funding Information This work is supported T32 HL07829, AHA 17SDG33700146 grants HK HL45638 grant YK ABM. abstract from Experimental Biology 2018 Meeting. There no full text article associated this published FASEB Journal