{"title":"Endothelial Glycocalyx, Mucin, and Glycan: A Hierarchical Synthesis From Molecular Building Blocks to Supramolecular Functional Barriers.","authors":"Hiroyuki Tomita, Akio Suzuki, Hideshi Okada","doi":"10.1111/micc.70069","DOIUrl":"10.1111/micc.70069","url":null,"abstract":"<p><p>Glycans encode molecular information, but the endothelial glycocalyx is an organized, multicomponent supramolecular structure whose architecture integrates glycan cues into coherent vascular responses in vivo. The vascular endothelial glycocalyx (eGCX) is a flow-conditioned, membrane-coupled surface layer that mediates mechanotransduction, selective permeability control under the revised Starling principle, and anticoagulant and anti-inflammatory functions central to hemostasis and thrombo-inflammation. However, \"glycocalyx\" is often conflated with individual glycans or mucins, causing conceptual drift in study design, assay selection, and biomarker interpretation. Here, we provide a hierarchical synthesis that distinguishes glycans as molecular building blocks, mucins as specialized, densely O-glycosylated glycoproteins (secreted gel-forming or transmembrane), and the eGCX as a supramolecular assembly organized around membrane-anchored proteoglycans bearing glycosaminoglycans and associated plasma constituents. Although glycocalyces exist on nearly all mammalian cells, this review focuses on the vascular eGCX. We explain why emergent eGCX functions-shear-dependent signaling, nitric oxide pathways, molecular sieving, and local regulation of coagulation-cannot be inferred from glycan motifs or mucin expression alone. We also clarify how commonly used readouts measure distinct biological processes: imaging-derived thickness and coverage, the perfused boundary region as a hydrodynamic exclusion index, and circulating shedding products such as syndecan-1, hyaluronan, and heparan sulfate as systemic markers of endothelial injury. Anchoring terminology to hierarchy and matching assays to targets should improve reproducibility and clinically meaningful translation in vascular disease, sepsis, trauma, and diabetes.</p>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"33 4","pages":"e70069"},"PeriodicalIF":2.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148005709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Guan Nan Liu, Chen Chen, Lin Xu, Wang Bo Yan, Jia Ning Gao, Ming Quan Lin, Yin Hua Zhang, Xiu Quan Quan
{"title":"Discordant and Worse Reactivity of Peripheral Microvasculature in Acute Ischemic Stroke Patients.","authors":"Guan Nan Liu, Chen Chen, Lin Xu, Wang Bo Yan, Jia Ning Gao, Ming Quan Lin, Yin Hua Zhang, Xiu Quan Quan","doi":"10.1111/micc.70058","DOIUrl":"10.1111/micc.70058","url":null,"abstract":"<p><strong>Background: </strong>Impaired opisthenar microvessel area (OMA) has been associated with adverse cardiac outcomes in acute myocardial infarction (AMI) patients. Here, we compared the characteristics of OMA of ischemic stroke (AIS) patients, National Institutes of Health Stroke Scale (NIHSS) positive, AIS recurrence, and AMI patients.</p><p><strong>Methods: </strong>OMA was investigated using optical coherence tomography (OCT) in AIS patients with mild or no neurological deficit (MND, NND) and recurrence or recurrence-free (RG, RFG). The characteristics of microvessel were compared to those of AMI patients. Brachial-ankle pulse wave velocity (baPWV) was also measured with Omron Instrument.</p><p><strong>Results: </strong>Compared to controls (Con), OMA, total and average vessel length (TVL, AVL) were smaller but End points (EPs) were greater in AIS at room temperature (RT). Both heat and cold stimulation (HS and CS) increased vessel length and area. However, significantly increased EPs and Lacunarity were observed at CS in AIS patients. As for the effect of neurological deficiency, OMA, TVL, and AVL were smaller, and EPs were markedly increased in MND with CS. OMA and TVL were smaller in the RG group at RT, but CS or HS did not change microvascular characteristics. Between AIS and AMI patients, baPWV was significantly greater in AIS, microvessel area and length were comparable between the two groups, and EPs were significantly increased in AIS. Furthermore, baPWV showed a positive correlation with OMA in CON, a negative correlation in AMI, but no correlation in AIS.</p><p><strong>Conclusions: </strong>Greater EPs and lacunarity of microvasculature are indicative of discordancy in AIS patients. Disrupted macrovascular-microvascular association in AIS suggests distinctive pathology to those of AMI.</p>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"33 4","pages":"e70058"},"PeriodicalIF":2.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147817132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Emanuel F Matias, Francisco M Vila-Real, Maria A Vieira-Coelho
{"title":"Microvascular Effects of Endocannabinoid Signaling in Sepsis: A Mechanistic and Systematic Review.","authors":"Emanuel F Matias, Francisco M Vila-Real, Maria A Vieira-Coelho","doi":"10.1111/micc.70062","DOIUrl":"10.1111/micc.70062","url":null,"abstract":"<p><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-guided systematic review of experimental studies assessing pharmacological modulation of ECS components under sepsis or endotoxemia conditions. Eleven studies met inclusion criteria, encompassing in vivo microcirculatory preparations and in vitro endothelial or immune-cell systems. Across models, three mechanistic domains consistently emerged: leukocyte-endothelial 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-endovanilloid signaling contributed to the stabilization of endothelial junctions and limitation of inflammatory hyperpermeability, whereas cannabinoid receptor 1 (CB1) signaling showed context-dependent influences on vascular tone and microvascular flow. These findings outline a coherent framework in which ECS activity-particularly through CB2-shapes 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.</p>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"33 4","pages":"e70062"},"PeriodicalIF":2.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13135129/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147817158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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