{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T06:11:45Z","timestamp":1775715105967,"version":"3.50.1"},"reference-count":66,"publisher":"American Physiological Society","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[2014,7,15]]},"abstract":"<jats:p> Inflammation-induced vascular endothelial dysfunction can allow plasma proteins to cross the vascular wall, causing edema. Proteins may traverse the vascular wall through two main pathways, the paracellular and transcellular transport pathways. Paracellular transport involves changes in endothelial cell junction proteins, while transcellular transport involves caveolar transcytosis. Since both processes are associated with filamentous actin formation, the two pathways are interconnected. Therefore, it is difficult to differentiate the prevailing role of one or the other pathway during various pathologies causing an increase in vascular permeability. Using a newly developed dual-tracer probing method, we differentiated transcellular from paracellular transport during hyperfibrinogenemia (HFg), an increase in fibrinogen (Fg) content. Roles of cholesterol and sphingolipids in formation of functional caveolae were assessed using a cholesterol chelator, methyl-\u03b2-cyclodextrin, and the de novo sphingolipid synthesis inhibitor myriocin. Fg-induced formation of functional caveolae was defined by association and colocalization of Na<jats:sup>+<\/jats:sup>-K<jats:sup>+<\/jats:sup>-ATPase and plasmalemmal vesicle-associated protein-1 with use of F\u00f6rster resonance energy transfer and total internal reflection fluorescence microscopy, respectively. HFg increased permeability of the endothelial cell layer mainly through the transcellular pathway. While M\u03b2CD blocked Fg-increased transcellular and paracellular transport, myriocin affected only transcellular transport. Less pial venular leakage of albumin was observed in myriocin-treated HFg mice. HFg induced greater formation of functional caveolae, as indicated by colocalization of Na<jats:sup>+<\/jats:sup>-K<jats:sup>+<\/jats:sup>-ATPase with plasmalemmal vesicle-associated protein-1 by F\u00f6rster resonance energy transfer and total internal reflection fluorescence microscopy. Our results suggest that elevated blood levels of Fg alter cerebrovascular permeability mainly by affecting caveolae-mediated transcytosis through modulation of de novo sphingolipid synthesis. <\/jats:p>","DOI":"10.1152\/ajpcell.00305.2013","type":"journal-article","created":{"date-parts":[[2014,5,15]],"date-time":"2014-05-15T09:12:34Z","timestamp":1400145154000},"page":"C169-C179","source":"Crossref","is-referenced-by-count":20,"title":["Sphingolipids affect fibrinogen-induced caveolar transcytosis and cerebrovascular permeability"],"prefix":"10.1152","volume":"307","author":[{"given":"Nino","family":"Muradashvili","sequence":"first","affiliation":[{"name":"Department of Physiology and Biophysics, School of Medicine, University of Louisville, Louisville, Kentucky;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Syed Jalal","family":"Khundmiri","sequence":"additional","affiliation":[{"name":"Kidney Disease Program, Department of Medicine, School of Medicine, University 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