{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:55:25Z","timestamp":1787018125730,"version":"build-2736575974"},"reference-count":39,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"12","license":[{"start":{"date-parts":[[2022,12,1]],"date-time":"2022-12-01T00:00:00Z","timestamp":1669852800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Stroke"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>\n                      Cerebral small vessel disease (SVD) is common in older people and causes lacunar stroke and vascular cognitive impairment. Risk factors include old age, hypertension and variants in the genes\n                      <jats:italic>COL4A1\/COL4A2<\/jats:italic>\n                      encoding collagen alpha-1(IV) and alpha-2(IV), here termed collagen-IV, which are core components of the basement membrane. We tested the hypothesis that increased vascular collagen-IV associates with clinical hypertension and with SVD in older persons and with chronic hypertension in young and aged primates and genetically hypertensive rats.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      We quantified vascular collagen-IV immunolabeling in small arteries in a cohort of older persons with minimal Alzheimer pathology (N=52; 21F\/31M, age 82.8\u00b16.95 years). We also studied archive tissue from young (age range 6.2\u20138.3 years) and older (17.0\u201322.7 years) primates (\n                      <jats:italic>M mulatta<\/jats:italic>\n                      ) and compared chronically hypertensive animals (18 months aortic stenosis) with normotensives. We also compared genetically hypertensive and normotensive rats (aged 10\u201312 months).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Collagen-IV immunolabeling in cerebral small arteries of older persons was negatively associated with radiological SVD severity (\u03c1: \u22120.427,\n                      <jats:italic>P<\/jats:italic>\n                      =0.005) but was not related to history of hypertension. General linear models confirmed the negative association of lower collagen-IV with radiological SVD (\n                      <jats:italic>P<\/jats:italic>\n                      &lt;0.017), including age as a covariate and either clinical hypertension (\n                      <jats:italic>P<\/jats:italic>\n                      &lt;0.030) or neuropathological SVD diagnosis (\n                      <jats:italic>P<\/jats:italic>\n                      &lt;0.022) as fixed factors. Reduced vascular collagen-IV was accompanied by accumulation of fibrillar collagens (types I and III) as indicated by immunogold electron microscopy. In young and aged primates, brain collagen-IV was elevated in older normotensive relative to young normotensive animals (\n                      <jats:italic>P<\/jats:italic>\n                      =0.029) but was not associated with hypertension. Genetically hypertensive rats did not differ from normotensive rats in terms of arterial collagen-IV.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Our cross-species data provide novel insight into sporadic SVD pathogenesis, supporting insufficient (rather than excessive) arterial collagen-IV in SVD, accompanied by matrix remodeling with elevated fibrillar collagen deposition. They also indicate that hypertension, a major risk factor for SVD, does not act by causing accumulation of brain vascular collagen-IV.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/strokeaha.122.037761","type":"journal-article","created":{"date-parts":[[2022,10,7]],"date-time":"2022-10-07T05:00:48Z","timestamp":1665118848000},"page":"3696-3705","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":30,"title":["Vascular Collagen Type-IV in Hypertension and Cerebral Small Vessel Disease"],"prefix":"10.1161","volume":"53","author":[{"given":"Apoorva A.","family":"Kumar","sequence":"first","affiliation":[{"name":"Molecular and Clinical Sciences Research Institute, St George\u2019s University of London, United Kingdom (A.A.K., N.Y., M.W., P.A., T.R.B., L.R.B., D.N.M., A.C.P., G.P., A.B.S., A.H.H.)."},{"name":"Neurology (A.A.K., A.C.P., A.H.H.), St George\u2019s University Hospitals NHS Foundation Trust, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9526-994X","authenticated-orcid":true,"given":"Natalie","family":"Yeo","sequence":"additional","affiliation":[{"name":"Molecular and Clinical Sciences Research Institute, St George\u2019s University of London, United Kingdom (A.A.K., N.Y., M.W., P.A., T.R.B., L.R.B., D.N.M., A.C.P., G.P., A.B.S., A.H.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6402-6494","authenticated-orcid":true,"given":"Max","family":"Whittaker","sequence":"additional","affiliation":[{"name":"Molecular and Clinical Sciences Research Institute, St George\u2019s University of London, United Kingdom (A.A.K., N.Y., M.W., P.A., T.R.B., L.R.B., D.N.M., A.C.P., G.P., A.B.S., A.H.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0311-8234","authenticated-orcid":true,"given":"Priya","family":"Attra","sequence":"additional","affiliation":[{"name":"Molecular and Clinical Sciences Research Institute, St George\u2019s University of London, United Kingdom (A.A.K., N.Y., M.W., P.A., T.R.B., L.R.B., D.N.M., A.C.P., G.P., A.B.S., A.H.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas R.","family":"Barrick","sequence":"additional","affiliation":[{"name":"Molecular and Clinical Sciences Research Institute, St George\u2019s University of London, United Kingdom (A.A.K., N.Y., M.W., P.A., T.R.B., L.R.B., D.N.M., A.C.P., G.P., A.B.S., A.H.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leslie R.","family":"Bridges","sequence":"additional","affiliation":[{"name":"Molecular and Clinical Sciences Research Institute, St George\u2019s University of London, United Kingdom (A.A.K., N.Y., M.W., P.A., T.R.B., L.R.B., D.N.M., A.C.P., G.P., A.B.S., A.H.H.)."},{"name":"Cellular Pathology (L.R.B.), St George\u2019s University Hospitals NHS Foundation Trust, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7189-7917","authenticated-orcid":true,"given":"Dennis W.","family":"Dickson","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Mayo Clinic, Jacksonville, FL (D.W.D., W.L.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6829-0962","authenticated-orcid":true,"given":"Margaret M.","family":"Esiri","sequence":"additional","affiliation":[{"name":"Nuffield Department of Clinical Neurosciences, Oxford University, United Kingdom (M.M.E., G.Z.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1133-3834","authenticated-orcid":true,"given":"Chad 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