{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T11:35:59Z","timestamp":1774956959009,"version":"3.50.1"},"reference-count":25,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2020,12,17]],"date-time":"2020-12-17T00:00:00Z","timestamp":1608163200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01HL072844, R21AI142649, R03AG059554, R03AA026516"],"award-info":[{"award-number":["R01HL072844, R21AI142649, R03AG059554, R03AA026516"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Ischemic stroke is a major cause of death among patients with systemic hypertension. The narrowing of the lumen of the brain vasculature contributes to the increased incidence of stroke. While hyalinosis represents the major pathological lesions contributing to vascular lumen narrowing and stroke, the pathogenic mechanism of brain vascular hyalinosis has not been well characterized. Thus, the present study examined the postmortem brain vasculature of human patients who died of ischemic stroke due to systemic hypertension. Hematoxylin and eosin staining and immunohistochemistry showed the occurrence of brain vascular hyalinosis with infiltrated plasma proteins along with the narrowing of the vasa vasorum and oxidative stress. Transmission electron microscopy revealed endothelial cell bulge protrusion into the vasa vasorum lumen and the occurrence of endocytosis in the vasa vasorum endothelium. The treatment of cultured microvascular endothelial cells with adrenaline also promoted the formation of the bulge as well as endocytic vesicles. The siRNA knockdown of sortin nexin-9 (a mediator of clathrin-mediated endocytosis) inhibited adrenaline-induced endothelial cell bulge formation. Adrenaline promoted protein-protein interactions between sortin nexin-9 and neural Wiskott\u2013Aldrich syndrome protein (a regulator of actin polymerization). Spontaneously hypertensive stroke-prone rats also exhibited lesions indicative of brain vascular hyalinosis, the endothelial cell protrusion into the lumen of the vasa vasorum, and endocytosis in vasa vasorum endothelial cells. We propose that endocytosis-dependent endothelial cell bulge protrusion narrows the vasa vasorum, resulting in ischemic oxidative damage to cerebral vessels, the formation of hyalinosis, the occurrence of ischemic stroke, and death in systemic hypertension patients.<\/jats:p>","DOI":"10.3390\/ijms21249611","type":"journal-article","created":{"date-parts":[[2020,12,17]],"date-time":"2020-12-17T10:42:47Z","timestamp":1608201767000},"page":"9611","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Vasa Vasorum Lumen Narrowing in Brain Vascular Hyalinosis in Systemic Hypertension Patients Who Died of Ischemic Stroke"],"prefix":"10.3390","volume":"21","author":[{"given":"Sergiy G.","family":"Gychka","sequence":"first","affiliation":[{"name":"Department of Pathological Anatomy N2, Bogomolets National Medical University, 01601 Kyiv, Ukraine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nataliia V.","family":"Shults","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Physiology, Georgetown University Medical Center, Washington, DC 20007, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sofia I.","family":"Nikolaienko","sequence":"additional","affiliation":[{"name":"Department of Pathological Anatomy N2, Bogomolets National Medical University, 01601 Kyiv, Ukraine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2301-7166","authenticated-orcid":false,"given":"Lucia","family":"Marcocci","sequence":"additional","affiliation":[{"name":"Department of Biochemical Sciences \u201cA. Rossi Fanelli\u201d, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2603-0182","authenticated-orcid":false,"given":"Nurefsan E.","family":"Sariipek","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Physiology, Georgetown University Medical Center, Washington, DC 20007, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8828-6493","authenticated-orcid":false,"given":"Vladyslava","family":"Rybka","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Physiology, Georgetown University Medical Center, Washington, DC 20007, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatiana A.","family":"Malysheva","sequence":"additional","affiliation":[{"name":"Department of Neuropathomorphology, Romodanov Neurosurgery Institute, 04050 Kyiv, Ukraine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vyacheslav A.","family":"Dibrova","sequence":"additional","affiliation":[{"name":"Department of Pathological Anatomy N2, Bogomolets National Medical University, 01601 Kyiv, Ukraine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuichiro J.","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Physiology, Georgetown University Medical Center, Washington, DC 20007, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander S.","family":"Gavrish","sequence":"additional","affiliation":[{"name":"Department of Pathological Anatomy N2, Bogomolets National Medical University, 01601 Kyiv, Ukraine"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e56","DOI":"10.1161\/CIR.0000000000000659","article-title":"Heart disease and stroke Statistics-2019 update: A report from the American Heart Association","volume":"139","author":"Benjamin","year":"2019","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1212\/WNL.0b013e318206ca1e","article-title":"Three-month stroke outcome: The European Registers of Stroke (EROS) investigators","volume":"76","author":"Heuschmann","year":"2011","journal-title":"Neurology"},{"key":"ref_3","first-page":"189","article-title":"Stroke burden in Ukraine: Analysis of the official stroke statistics and overview of population-based epidemiological studies","volume":"13","author":"Filipets","year":"2014","journal-title":"Clin. 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