{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T10:15:00Z","timestamp":1779963300298,"version":"3.53.1"},"reference-count":40,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Microcirculation"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Microvascular dysfunction is a central determinant of organ failure in sepsis, reflecting early endothelial activation, increased permeability, and impaired capillary perfusion. Experimental evidence suggests that the endocannabinoid system (ECS) modulates these immunovascular processes, yet mechanistic insights remain dispersed across heterogeneous models. We conducted a PRISMA\u2010guided systematic review of experimental studies assessing pharmacological modulation of ECS components under sepsis or endotoxemia conditions. Eleven studies met inclusion criteria, encompassing in\u00a0vivo microcirculatory preparations and in\u00a0vitro endothelial or immune\u2010cell systems. Across models, three mechanistic domains consistently emerged: leukocyte\u2010endothelial adhesion, endothelial barrier integrity, and vascular reactivity. Among these, cannabinoid receptor 2 (CB2) activation produced the most reproducible effects, reducing adhesion molecule expression and attenuating leukocyte recruitment. Endocannabinoid\u2010endovanilloid signaling contributed to the stabilization of endothelial junctions and limitation of inflammatory hyperpermeability, whereas cannabinoid receptor 1 (CB1) signaling showed context\u2010dependent influences on vascular tone and microvascular flow. These findings outline a coherent framework in which ECS activity\u2014particularly through CB2\u2014shapes early microvascular responses to sepsis. Standardized and clinically relevant models will be essential to determine whether targeting ECS pathways can yield effective strategies to protect the microcirculation during sepsis.<\/jats:p>","DOI":"10.1111\/micc.70062","type":"journal-article","created":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T06:05:47Z","timestamp":1777701947000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Microvascular Effects of Endocannabinoid Signaling in Sepsis: A Mechanistic and Systematic Review"],"prefix":"10.1111","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2507-4212","authenticated-orcid":false,"given":"Emanuel F.","family":"Matias","sequence":"first","affiliation":[{"name":"Unit of Pharmacology and Therapeutics, Department of Biomedicine, Faculty of Medicine University of Porto  Porto Portugal"},{"name":"Center for Drug Discovery and Innovative Medicines (MedInUP)\/RISE\u2010Health: Health Research 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