{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T12:49:25Z","timestamp":1789130965865,"version":"build-2803163510"},"reference-count":93,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T00:00:00Z","timestamp":1781222400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Natural Science Foundation of Chongqing, China","award":["CSTB2022NSCQ-MSX0111"],"award-info":[{"award-number":["CSTB2022NSCQ-MSX0111"]}]},{"DOI":"10.13039\/501100004374","name":"Chongqing Medical University","doi-asserted-by":"publisher","award":["TY202301"],"award-info":[{"award-number":["TY202301"]}],"id":[{"id":"10.13039\/501100004374","id-type":"DOI","asserted-by":"publisher"}]},{"award":["TY202301"],"award-info":[{"award-number":["TY202301"]}],"id":[{"id":"https:\/\/ror.org\/017z00e58","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCDD"],"abstract":"<jats:p>Acute cardiovascular events driven by atherosclerosis primarily originate from thrombosis triggered by vulnerable plaque rupture or endothelial erosion. Endothelial barrier destabilization\u2014characterized by glycocalyx impairment, intercellular junction disassembly, and abnormal cytoskeletal tension\u2014is a core upstream pathological stage that promotes atherogenic lipoprotein leakage, inflammatory cell infiltration, and matrix degradation. Hemodynamics, primarily through wall shear stress (WSS), shape the spatial distribution and plaque phenotypes of atherosclerosis; notably, low or oscillatory shear stress is associated with, and in experimental systems can promote, pro-inflammatory, pro-oxidant and pro-permeability endothelial phenotypes that contribute to plaque initiation and vulnerability. Conversely, regular exercise training, as an intervention that modulates hemodynamics, is widely suggested to promote anti-inflammatory, antioxidant, and antithrombotic endothelial phenotypes by significantly increasing antegrade shear stress and reducing detrimental retrograde\/oscillatory shear stress. With a central focus on the axis of \u201cexercise-shear stress-glycocalyx-cytoskeleton\/junction-permeability-plaque stability,\u201d this review integrates evidence from in vitro flow chambers, animal models and human studies to critically discuss: (1) the spatiotemporal heterogeneity of WSS and its relationship with plaque vulnerability; (2) the composition, barrier function, and plasticity of the glycocalyx as the primary interface for shear stress; (3) the mechanosensory complexes at the glycocalyx and junctions that transduce shear stimuli to protective pathways such as Phosphoinositide 3-kinase (PI3K)-Akt-endothelial nitric oxide synthase (eNOS) and Kr\u00fcppel-like factor 2 (KLF2), thereby stabilizing adherens\/tight junctions; (4) how improved barrier homeostasis promotes the maintenance of the fibrous cap collagen scaffold by reducing lipoprotein leakage and dampening the inflammation\u2013matrix metalloproteinase (MMP) axis. Finally, this review highlights the boundary conditions of the biological effects of shear stress: low\/oscillatory shear stress is primarily associated with plaque initiation and susceptible sites, whereas focal, extremely high WSS in established stenotic lesions may contribute to late-stage high-risk remodeling. Therefore, the protective hemodynamic adaptations induced by exercise should not be simply equated with the pathologically high WSS found at stenotic sites.<\/jats:p>","DOI":"10.3390\/jcdd13060265","type":"journal-article","created":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T09:49:51Z","timestamp":1781257791000},"page":"265","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Exercise-Induced Shear Stress, Endothelial Glycocalyx Remodeling, and Atherosclerotic Plaque Stability: A Mechanistic Review"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-3805-2215","authenticated-orcid":false,"given":"Zihong","family":"Qi","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering, Hong Kong Polytechnic University, Hong Kong 999077, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenggang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Sports Department, Harbin Institute of Technology, Harbin 150000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huilin","family":"Shi","sequence":"additional","affiliation":[{"name":"School of Sport and Health, Shenyang Sport University, Shenyang 110000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Li","sequence":"additional","affiliation":[{"name":"School of Public Health, Chongqing Medical University, Chongqing 400016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuqing","family":"Xia","sequence":"additional","affiliation":[{"name":"The Second Clinical College, Chongqing Medical University, Chongqing 400016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofeng","family":"Yan","sequence":"additional","affiliation":[{"name":"University of Leicester Joint Institute, Chongqing Medical University, Chongqing 400016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-5366-338X","authenticated-orcid":false,"given":"Xiyan","family":"Zhou","sequence":"additional","affiliation":[{"name":"The Second Clinical College, Chongqing Medical University, Chongqing 400016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-8711-2960","authenticated-orcid":false,"given":"Jiaqi","family":"Ling","sequence":"additional","affiliation":[{"name":"School of Public Health, Chongqing Medical University, Chongqing 400016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guochun","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Exercise Medicine, Chongqing Medical University, Chongqing 400016, China"},{"name":"Division of Sports Science and Physical Education, Tsinghua University, Beijing 100084, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"C13","DOI":"10.1016\/j.jacc.2005.10.065","article-title":"Pathology of the vulnerable plaque","volume":"47","author":"Virmani","year":"2006","journal-title":"J. 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