{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T22:41:21Z","timestamp":1775083281792,"version":"3.50.1"},"reference-count":47,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"12","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2017,12,8]]},"abstract":"<jats:sec>\n            <jats:title>\n              <jats:underline>Rationale:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>Cryptogenic strokes, those of unknown cause, have been estimated as high as 30% to 40% of strokes. Inflammation has been suggested as a critical etiologic factor. However, there is lack of experimental evidence.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Objective:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>In this study, we investigated inflammation-associated stroke using a mouse model that developed spontaneous stroke because of myeloid deficiency of TGF-\u03b2 (transforming growth factor-\u03b2) signaling.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Methods and Results:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>\n              We report that mice with deletion of\n              <jats:italic>Tgfbr2<\/jats:italic>\n              in myeloid cells (\n              <jats:italic>Tgfbr2<\/jats:italic>\n              <jats:sup>Myeko<\/jats:sup>\n              ) developed cerebrovascular inflammation in the absence of significant pathology in other tissues, culminating in stroke and severe neurological deficits with 100% penetrance. The stroke phenotype can be transferred to syngeneic wild-type mice via\n              <jats:italic>Tgfbr2<\/jats:italic>\n              <jats:sup>Myeko<\/jats:sup>\n              bone marrow transplant and can be rescued in Tgfbr2\n              <jats:sup>Myeko<\/jats:sup>\n              mice with wild-type bone marrow. The underlying mechanisms involved an increased type 1 inflammation and cerebral endotheliopathy, characterized by elevated NF-\u03baB (nuclear factor-\u03baB) activation and TNF (tumor necrosis factor) production by myeloid cells. A high-fat diet accelerated stroke incidence. Anti-TNF treatment, as well as metformin and methotrexate, which are associated with decreased stroke risk in population studies, delayed stroke occurrence.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Conclusions:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>Our studies show that TGF-\u03b2 signaling in myeloid cells is required for maintenance of vascular health and provide insight into inflammation-mediated cerebrovascular disease and stroke.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circresaha.116.310349","type":"journal-article","created":{"date-parts":[[2017,10,19]],"date-time":"2017-10-19T09:15:35Z","timestamp":1508404535000},"page":"1360-1369","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":21,"title":["Attenuation of Myeloid-Specific TGF\u03b2 Signaling Induces Inflammatory Cerebrovascular Disease and Stroke"],"prefix":"10.1161","volume":"121","author":[{"given":"M. Christine","family":"Hollander","sequence":"first","affiliation":[{"name":"From the Laboratory of Cancer Biology and Genetics, National Cancer Institute (M.C.H., H.I., Z.X., L.Y.), Clinical Stroke Cause and Development, National Institute of Neurological Disorders and Stroke (L.L.L., J.M., J.H.), Center for Molecular Medicine, National Institute of Heart Lung and Blood (D.Y., M.B.), Neuropathology, National Institute of Neurological Disorders and Stroke (A.R.-C.), and Bioinformatics, Center for Cancer Research, National Cancer Institute (A.S.M.), National Institutes of..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lawrence L.","family":"Latour","sequence":"additional","affiliation":[{"name":"From the Laboratory of Cancer Biology and Genetics, National Cancer Institute (M.C.H., H.I., Z.X., L.Y.), Clinical Stroke Cause and Development, National Institute of Neurological Disorders and Stroke (L.L.L., J.M., J.H.), Center for Molecular Medicine, National Institute of Heart Lung and Blood (D.Y., M.B.), Neuropathology, National Institute of Neurological Disorders and Stroke (A.R.-C.), and Bioinformatics, Center for Cancer Research, National Cancer Institute (A.S.M.), National Institutes of..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dan","family":"Yang","sequence":"additional","affiliation":[{"name":"From the Laboratory of Cancer Biology and Genetics, National Cancer Institute (M.C.H., H.I., Z.X., L.Y.), Clinical Stroke Cause and Development, National Institute of Neurological Disorders and Stroke (L.L.L., J.M., J.H.), Center for Molecular Medicine, National Institute of Heart Lung and Blood (D.Y., M.B.), Neuropathology, National Institute of Neurological Disorders and Stroke (A.R.-C.), and Bioinformatics, Center for Cancer Research, National Cancer Institute (A.S.M.), National Institutes of..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroki","family":"Ishii","sequence":"additional","affiliation":[{"name":"From the Laboratory of Cancer Biology and Genetics, National Cancer Institute (M.C.H., H.I., Z.X., L.Y.), Clinical Stroke Cause and Development, National Institute of Neurological Disorders and Stroke (L.L.L., J.M., J.H.), Center for Molecular Medicine, National Institute of Heart Lung and Blood (D.Y., M.B.), Neuropathology, National Institute of Neurological Disorders and Stroke (A.R.-C.), and Bioinformatics, Center for Cancer Research, National Cancer Institute (A.S.M.), National Institutes of..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhiguang","family":"Xiao","sequence":"additional","affiliation":[{"name":"From the Laboratory of Cancer Biology and Genetics, National Cancer Institute (M.C.H., H.I., Z.X., L.Y.), Clinical Stroke Cause and Development, National Institute of Neurological Disorders and Stroke (L.L.L., J.M., J.H.), Center for Molecular Medicine, National Institute of Heart Lung and Blood (D.Y., M.B.), Neuropathology, National Institute of Neurological Disorders and Stroke (A.R.-C.), and Bioinformatics, Center for Cancer Research, National Cancer Institute (A.S.M.), National Institutes of..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yongfen","family":"Min","sequence":"additional","affiliation":[{"name":"From the Laboratory of Cancer Biology and Genetics, National Cancer Institute (M.C.H., H.I., Z.X., L.Y.), Clinical Stroke Cause and Development, National Institute of Neurological Disorders and Stroke (L.L.L., J.M., J.H.), Center for Molecular Medicine, National Institute of Heart Lung and Blood (D.Y., M.B.), Neuropathology, National Institute of Neurological Disorders and Stroke (A.R.-C.), and Bioinformatics, Center for Cancer Research, National Cancer Institute (A.S.M.), National Institutes 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(L.L.L., J.M., J.H.), Center for Molecular Medicine, National Institute of Heart Lung and Blood (D.Y., M.B.), Neuropathology, National Institute of Neurological Disorders and Stroke (A.R.-C.), and Bioinformatics, Center for Cancer Research, National Cancer Institute (A.S.M.), National Institutes of..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anand S.","family":"Merchant","sequence":"additional","affiliation":[{"name":"From the Laboratory of Cancer Biology and Genetics, National Cancer Institute (M.C.H., H.I., Z.X., L.Y.), Clinical Stroke Cause and Development, National Institute of Neurological Disorders and Stroke (L.L.L., J.M., J.H.), Center for Molecular Medicine, National Institute of Heart Lung and Blood (D.Y., M.B.), Neuropathology, National Institute of Neurological Disorders and Stroke (A.R.-C.), and Bioinformatics, Center for Cancer Research, National Cancer Institute (A.S.M.), National Institutes 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Charles","family":"Lin","sequence":"additional","affiliation":[{"name":"From the Laboratory of Cancer Biology and Genetics, National Cancer Institute (M.C.H., H.I., Z.X., L.Y.), Clinical Stroke Cause and Development, National Institute of Neurological Disorders and Stroke (L.L.L., J.M., J.H.), Center for Molecular Medicine, National Institute of Heart Lung and Blood (D.Y., M.B.), Neuropathology, National Institute of Neurological Disorders and Stroke (A.R.-C.), and Bioinformatics, Center for Cancer Research, National Cancer Institute (A.S.M.), National Institutes of..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Hallenbeck","sequence":"additional","affiliation":[{"name":"From the Laboratory of Cancer Biology and Genetics, National Cancer Institute (M.C.H., H.I., Z.X., L.Y.), Clinical Stroke Cause and Development, National Institute of Neurological Disorders and Stroke (L.L.L., J.M., J.H.), Center for Molecular Medicine, National Institute of Heart Lung and Blood (D.Y., M.B.), Neuropathology, National Institute of Neurological Disorders and Stroke (A.R.-C.), and Bioinformatics, Center for Cancer Research, National Cancer Institute (A.S.M.), National Institutes of..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manfred","family":"Boehm","sequence":"additional","affiliation":[{"name":"From the Laboratory of Cancer Biology and Genetics, National Cancer Institute (M.C.H., H.I., Z.X., L.Y.), Clinical Stroke Cause and Development, National Institute of Neurological Disorders and Stroke (L.L.L., J.M., J.H.), Center for Molecular Medicine, National Institute of Heart Lung and Blood (D.Y., M.B.), Neuropathology, National Institute of Neurological Disorders and Stroke (A.R.-C.), and Bioinformatics, Center for Cancer Research, National Cancer Institute (A.S.M.), National Institutes 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