{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T13:04:42Z","timestamp":1789391082996,"version":"build-2803163510"},"reference-count":192,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T00:00:00Z","timestamp":1789171200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000005","name":"DoD","doi-asserted-by":"publisher","award":["HT9425-23-1-0524"],"award-info":[{"award-number":["HT9425-23-1-0524"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"award":["HT9425-23-1-0524"],"award-info":[{"award-number":["HT9425-23-1-0524"]}],"id":[{"id":"https:\/\/ror.org\/0447fe631","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Traditionally, chronic wounds including diabetic foot ulcers (DFUs), pressure ulcers (PUs), venous leg ulcers (VLUs), arterial ulcers, inflammatory and autoimmune-associated ulcers, infected chronic wounds, and non-healing post-surgical wounds are treated as localized diseases of skin and soft tissue damage. However, these lesions are increasingly acknowledged as chronic inflammatory states with consequences extending beyond the wound bed and often arising in the setting of systemic dysfunction. Across wound types, shared features include persistent inflammation, oxidative stress, endothelial dysfunction, immune imbalance, protease dysregulation, infection or biofilm burden, metabolic disturbance, and impaired regenerative signaling. These abnormalities may promote systemic cytokine release, vascular dysfunction, neurohumoral activation, oxidative injury, and maladaptive remodeling. Cardiac dysfunction is already known to impair wound healing. In contrast, whether chronic non-healing wounds are associated with or may contribute to cardiac damage resulting in heart failure remains insufficiently defined. Emerging epidemiologic and mechanistic evidence suggests that chronic non-healing wounds may amplify cardiovascular stress, particularly in vulnerable patients with diabetes, obesity, frailty, kidney disease, or pre-existing vascular disease. This narrative review explores the conceptual hypothesis that chronic non-healing wounds may contribute to systemic cardiovascular stress and cardiac dysfunction. It integrates clinical and mechanistic opportunities, outlines potential pathways, including extracellular vesicle (EV) signaling, and highlights key knowledge gaps and therapeutic implications in the wound\u2013heart axis.<\/jats:p>","DOI":"10.3390\/ijms27188138","type":"journal-article","created":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T12:09:51Z","timestamp":1789387791000},"page":"8138","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Wound\u2013Heart Axis: Can Chronic Wounds Contribute to Cardiac Dysfunction?"],"prefix":"10.3390","volume":"27","author":[{"given":"Preeti K.","family":"Chaudhary","sequence":"first","affiliation":[{"name":"Molecular Cardiology Research Institute, Tufts Medical Center, Boston, MA 02111, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Howard H.","family":"Chen","sequence":"additional","affiliation":[{"name":"Molecular Cardiology Research Institute, Tufts Medical Center, Boston, MA 02111, USA"},{"name":"Department of Medicine, Tufts University, Boston, MA 02111, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lakshmi","family":"Pulakat","sequence":"additional","affiliation":[{"name":"Molecular Cardiology Research Institute, Tufts Medical Center, Boston, MA 02111, USA"},{"name":"Department of Medicine, Tufts University, Boston, MA 02111, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Riaz, M., Iqbal, M.Z., Klar, A.S., and Biedermann, T. 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