{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T05:53:51Z","timestamp":1791179631614,"version":"4.1.0"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:00:00Z","timestamp":1791158400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cardiovasc. Med."],"abstract":"<jats:p>Osteoarthritis (OA) may be more than simply a reflection of aging; it could represent a symptom of underlying vascular disease processes with serious consequences for health and quality of life. The association of OA with other conditions like cardiovascular disease (CVD) suggests OA may be partially systemic and metabolic in nature. As such, this connection underscores the value of exploring the biochemical parallels between articular joints and the endothelial glycocalyx, the protective lining of blood vessels. N-acetylglucosamine may be central to this link because both articular cartilage and the endothelial glycocalyx depend on N-acetylglucosamine-containing structures. A better understanding of the pathophysiology linking OA and CVD provides the basis for the present hypothesis. Hypothesis: A reduction in available or utilized levels of N-acetylglucosamine results in a parallel degradation of articular cartilage and the endothelial glycocalyx. This would result in a shared glycan-dependent mechanism linking the pathogenesis of OA to increased cardiovascular risk. Implications: OA could serve as an early clinical marker for vascular dysfunction and potentially identify glycocalyx-targeted interventions as a new area of investigation for therapies to reduce both OA and CVD. The novelty of this research hypothesis is based on suggesting that N-acetylglucosamine-dependent glycan insufficiency is a unified mechanism connecting cartilage degeneration with vascular endothelial damage.<\/jats:p>","DOI":"10.3389\/fcvm.2026.1903797","type":"journal-article","created":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T05:32:06Z","timestamp":1791178326000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Osteoarthritis as a marker and potential contributor to cardiovascular risk: a glycocalyx\u2013cartilage axis hypothesis"],"prefix":"10.3389","volume":"13","author":[{"given":"Willem","family":"Wassenaar","sequence":"first","affiliation":[{"name":"Wellesley Therapeutics Inc.","place":["Toronto, ON, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,10,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1016\/j.joca.2009.08.003","article-title":"Depth-wise progression of osteoarthritis in human articular cartilage: investigation of composition, structure and biomechanics","volume":"18","author":"Saarakkala","year":"2010","journal-title":"Osteoarthritis Cartilage"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1771","DOI":"10.1016\/j.joca.2017.07.024","article-title":"The longitudinal relationship between hand, hip and knee osteoarthritis and cardiovascular events: a population-based cohort study","volume":"25","author":"Kendzerska","year":"2017","journal-title":"Osteoarthritis Cartilage"},{"key":"B3","first-page":"S223","article-title":"The burden of osteoarthritis: clinical and quality-of-life issues","volume":"15","author":"Moskowitz","year":"2009","journal-title":"Am J Manag Care"},{"key":"B4","doi-asserted-by":"publisher","first-page":"2350","DOI":"10.1016\/j.jacc.2023.11.007","article-title":"Global burden of cardiovascular diseases and risks, 1990\u20132022","volume":"82","author":"Mensah","year":"2023","journal-title":"J Am Coll Cardiol"},{"key":"B5","doi-asserted-by":"publisher","first-page":"1821","DOI":"10.1093\/ije\/dyy187","article-title":"Osteoarthritis and risk of mortality in the USA: a population-based cohort study","volume":"47","author":"Mendy","year":"2018","journal-title":"Int J Epidemiol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"2777","DOI":"10.1038\/s41598-023-29581-1","article-title":"Association between knee osteoarthritis and the risk of cardiovascular disease and the synergistic adverse effects of lack of exercise","volume":"13","author":"Park","year":"2023","journal-title":"Sci Rep"},{"key":"B7","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1007\/s00424-007-0212-8","article-title":"The endothelial glycocalyx: composition, functions, and visualization","volume":"454","author":"Reitsma","year":"2007","journal-title":"Pfl\u00fcgers Arch"},{"key":"B8","first-page":"232","article-title":"Chapter 16 Proteoglycans and sulfated glycosaminoglycans","volume-title":"Essentials of Glycobiology","author":"Esko","year":"2009"},{"key":"B9","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1194\/jlr.P800025-JLR200","article-title":"Partial recovery of the endothelial glycocalyx upon rosuvastatin therapy in patients with heterozygous familial hypercholesterolemia","volume":"50","author":"Meuwese","year":"2009","journal-title":"J Lipid Res"},{"key":"B10","doi-asserted-by":"publisher","first-page":"890","DOI":"10.1007\/s12265-021-10180-2","article-title":"Impaired endothelial glycocalyx predicts adverse outcome in subjects without overt cardiovascular disease: a 6-year follow-up study","volume":"15","author":"Ikonomidis","year":"2022","journal-title":"J Cardiovasc Transl Res"},{"key":"B11","doi-asserted-by":"publisher","first-page":"5092","DOI":"10.1093\/emboj\/19.19.5092","article-title":"Decreased UDP-GlcNAc levels abrogate proliferation control in EMeg32-deficient cells","volume":"19","author":"Boehmelt","year":"2000","journal-title":"EMBO J"},{"key":"B12","doi-asserted-by":"publisher","first-page":"4706","DOI":"10.1016\/S0021-9258(19)67706-9","article-title":"Discovery of a metabolic pathway mediating glucose-induced desensitization of the glucose transport system. 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