YAP binding sustained STAT3 in the nucleus to enhance the latter's transcriptional activity and promote angiogenesis via regulation of angiopoietin-2.
Rationale: Atherosclerosis preferentially occurs at specific sites of the vasculature where endothelial cells (ECs) are exposed to disturbed blood flow. Translocation of integrin α5 to lipid rafts promotes integrin activation and ligation, which is critical for oscillatory shear stress (OSS)-induced EC activation. However, the underlying mechanism of OSS promoted integrin α5 lipid raft translocation has remained largely unknown. Objective: The objective of this study was to specify the mechanotransduction mechanism of OSS-induced integrin α5 translocation and subsequent EC activation. Methods and Results: Mass spectrometry studies identified endothelial ANXA2 (annexin A2) as a potential carrier allowing integrin α5β1 to traffic in response to OSS. Interference by siRNA of AnxA2 in ECs greatly decreased OSS-induced integrin α5β1 translocation to lipid rafts, EC activation, and monocyte adhesion. Pharmacological and genetic inhibition of PTP1B (protein tyrosine phosphatase 1B) blunted OSS-induced integrin α5β1 activation, which is dependent on Piezo1-mediated calcium influx in ECs. Furthermore, ANXA2 was identified as a direct substrate of activated PTP1B by mass spectrometry. Using bioluminescence resonance energy transfer assay, PTP1B-dephosphorylated ANXA2 at Y24 was found to lead to conformational freedom of the C-terminal core domain from the N-terminal domain of ANXA2. Immunoprecipitation assays showed that this unmasked ANXA2-C-terminal core domain specifically binds to an integrin α5 nonconserved cytoplasmic domain but not β1. Importantly, ectopic lentiviral overexpression of an ANXA2 Y24F mutant increased and shRNA against Ptp1B decreased integrin α5β1 ligation, inflammatory signaling, and progression of plaques at atheroprone sites in apolipoprotein E ( ApoE ) −/− mice. However, the antiatherosclerotic effect of Ptp1B shRNA was abolished in AnxA2 −/− ApoE −/− mice. Conclusions: Our data elucidate a novel endothelial mechanotransduction molecular mechanism linking atheroprone flow and activation of integrin α5β1, thereby identifying a class of potential therapeutic targets for atherosclerosis. Graphic Abstract: An graphic abstract is available for this article.
The electrochemical advanced oxidation process (EAOP) has gained popularity in the field of water purification. During the EAOP, it is in the boundary layer of the anode–solution interface that organic pollutants are oxidized by hydroxyl radicals (•OH) produced from water oxidation. Applying current to an anode dissipates heat to the surroundings according to Joule’s law, leading to an interfacial temperature that is much higher than that of the bulk solution, which is known as the “interfacial Joule heating” (IJH) effect. The modeling and experimental results show that the IJH effect had an inevitable consequence for the activity of •OH, rate constants, and mass transport within the boundary layer. The interfacial temperature could be increased from 25 to 70.2 °C, a value mostly doubling that of the bulk solution (33.6 °C) at the end of a 120 min electrolysis (10 mA cm–2). Correspondingly, the •OH concentration available for oxidation of organic pollutants was much lower than that calculated at a constant temperature of 25 °C probably due to H2O2 formation via •OH dimerization. The enhanced •OH diffusion resulting from strengthened molecular thermodynamic movement and decreased kinematic viscosity of the solution also drove •OH to move far from the anode surface and thus extended the maximum thickness of the boundary layer. The oxidation rate was positively correlated to the interfacial temperature, the activation energy, and the number of activated molecules, indicated by a 1.57–2.28-fold increase depending on the target organic compounds. The finding of the IJH effect prompts a re-examination of the literature based on a realistic rather than a constant temperature (e.g., 20–30 °C), the case reflected in a number of prior studies that does not exist virtually, and reconsideration of behaviors that can be attributed to the change in temperature during EAOP.
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