{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T10:59:53Z","timestamp":1789988393416,"version":"4.0.1"},"reference-count":29,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T00:00:00Z","timestamp":1789689600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Major Medical Research Project of Hongkou District Health Commission","award":["Hongwei 2401-08"],"award-info":[{"award-number":["Hongwei 2401-08"]}]},{"name":"Shanghai 2025 Science and Technology Industry High-Quality Development Plan \u201cInnovative Drug and Medical Device Application Demonstration\u201d Project","award":["24SF1902500"],"award-info":[{"award-number":["24SF1902500"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Hemodynamic shear stress is a critical mechanical determinant of endothelial homeostasis, yet the mechanosensitive pathways governing metabolic reprogramming remain incompletely understood. Apolipoprotein A-I binding protein (AIBP) regulates cholesterol metabolism, but its role in endothelial mechanotransduction is unknown. Here, we investigated how shear stress modulates AIBP expression to direct human brain microvascular endothelial cell (HBMEC) function via vascular endothelial growth factor (VEGF)-dependent glycolytic reprogramming. HBMECs were subjected to laminar shear stress (1 Pa) with or without the mechanosensitive channel inhibitor GsMTx4. We utilized loss-of-function approaches (shRNA targeting AIBP and VEGF), metabolic assays (metabolite quantification, Western blotting of glycolytic enzymes), and functional assays (EdU proliferation, Transwell migration, tube formation, and apoptosis analysis). Laminar shear stress significantly downregulated AIBP levels via mechanosensitive channel activation. Downregulation or genetic silencing of AIBP stabilized HIF-1\u03b1, relieving constitutive repression of VEGF and activating downstream Akt and ERK1\/2 signaling. This axis drove glycolytic reprogramming\u2014evidenced by coordinated upregulation of GLUT1, HK2, PFK-A, PKM2, PTBP1, and LDHA, and accumulation of L(+)-lactate and pyruvate\u2014which enhanced proliferation, migration, and tube formation while attenuating apoptosis. Pharmacological inhibition with GsMTx4 prevented shear-induced AIBP downregulation and subsequent metabolic activation. Crucially, simultaneous knockdown of VEGF abolished the glycolytic and phenotypic shifts induced by AIBP deficiency. AIBP functions as a novel mechanosensitive effector in endothelial cells. Shear stress-induced, channel-dependent downregulation of AIBP orchestrates endothelial activation strictly through VEGF-mediated glycolytic reprogramming, identifying a key mechano-metabolic coupling mechanism in vascular regulation.<\/jats:p>","DOI":"10.3390\/biology15181650","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T09:01:38Z","timestamp":1789981298000},"page":"1650","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Fluid Shear Stress Drives Endothelial Glycolytic Reprogramming via an AIBP\/VEGF Axis"],"prefix":"10.3390","volume":"15","author":[{"given":"Linhua","family":"Zhou","sequence":"first","affiliation":[{"name":"Orient Vascular Innovation Institute, University of Shanghai for Science and Technology, Shanghai 200093, China"},{"name":"Department of Clinical Neurology Medical Center, 411 Hospital, Shanghai University, Shanghai 200081, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"given":"Xiaowu","family":"He","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurology Medical Center, 411 Hospital, Shanghai University, Shanghai 200081, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"}]},{"given":"Yaowu","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurology Medical Center, 411 Hospital, Shanghai University, Shanghai 200081, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"given":"Yanpeng","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurology Medical Center, 411 Hospital, Shanghai University, Shanghai 200081, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"}]},{"given":"Yiting","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurology Medical Center, 411 Hospital, Shanghai University, Shanghai 200081, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"}]},{"given":"Qi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurology Medical Center, 411 Hospital, Shanghai University, Shanghai 200081, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1152\/physrev.00047.2009","article-title":"Effects of disturbed flow on vascular endothelium: Pathophysiological basis and clinical perspectives","volume":"91","author":"Chiu","year":"2011","journal-title":"Physiol. 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