{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T19:28:55Z","timestamp":1770665335300,"version":"3.49.0"},"reference-count":35,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"12","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2010,12]]},"abstract":"<jats:p>\n            <jats:bold>\n              <jats:italic>Objective\u2014<\/jats:italic>\n            <\/jats:bold>\n            To use protein kinase C (PKC) \u03b4\u2013knockout mice to investigate the role of PKC\u03b4 in lesion development and to understand the underlying mechanism of the vascular disease.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Methods and Results\u2014<\/jats:italic>\n            <\/jats:bold>\n            PKC\u03b4 functions as a signal transducer mediating several essential functions of cell proliferation and apoptosis. However, the effect of PKC\u03b4 on neointimal formation in wire-injured vessels is unknown. Three weeks after wire injury of femoral arteries, neointimal lesions were significantly increased in PKC\u03b4\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            mice compared with PKC\u03b4\n            <jats:sup>+\/+<\/jats:sup>\n            animals. Immunohistochemical staining revealed that total numbers of smooth muscle cells and macrophages in the lesions of PKC\u03b4\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            mice were markedly elevated without changing the ratio of these 2 cell types. To further elucidate the mechanisms of PKC\u03b4-mediated increase in the lesion, an in vivo endothelial migration model was established to evaluate endothelial wound healing after wire injury. Data showed that reendothelialization of the injured vessel was markedly delayed in PKC\u03b4\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            mice; this coincided with more severe intimal hyperplasia. Migration of endothelial cells cultivated from cardiac tissue was markedly reduced in the absence of PKC\u03b4, whereas no difference in proliferation or apoptosis was detected. Inhibition of PKC\u03b4 activity or protein expression by small hairpin RNA (shRNA) in cultured endothelial cells confirmed the defective migratory phenotype. Interestingly, vasohibin-1, an antiangiogenesis protein, was elevated in endothelial cells derived from PKC\u03b4\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            mice, which was mainly because of delayed protein degradation mediated by PKC\u03b4. Downregulation of vasohibin-1 restored the migration rate of PKC\u03b4\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            endothelial cells to a similar level as PKC\u03b4\n            <jats:sup>+\/+<\/jats:sup>\n            cells.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Conclusion\u2014<\/jats:italic>\n            <\/jats:bold>\n            PKC\u03b4 deficiency enhances neointimal formation, which is associated with delayed reendothelialization and involves increased cellular vasohibin-1 accumulation.\n          <\/jats:p>","DOI":"10.1161\/atvbaha.110.215723","type":"journal-article","created":{"date-parts":[[2010,10,1]],"date-time":"2010-10-01T03:05:21Z","timestamp":1285902321000},"page":"2467-2474","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":21,"title":["Protein Kinase C\u03b4 Deficiency Accelerates Neointimal Lesions of Mouse Injured Artery Involving Delayed Reendothelialization and Vasohibin-1 Accumulation"],"prefix":"10.1161","volume":"30","author":[{"given":"Xue","family":"Bai","sequence":"first","affiliation":[{"name":"From the Department of Physiology (X.B. and X.W.), Peking University Health Science Center, Beijing, China; the Cardiovascular Division (X.B., A.M., Y.H., L.Z., A.I., O.H., and Q.X.), King\u2019s College London British Heart Foundation Centre, London, England; the Department of Vascular Biology (Y.S.), Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan; the Bywaters Centre for Vascular Inflammation (J.C.M.), Imperial College, Hammersmith Hospital, London, England."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andriana","family":"Margariti","sequence":"additional","affiliation":[{"name":"From the Department of Physiology (X.B. and X.W.), Peking University Health Science Center, Beijing, China; the Cardiovascular Division (X.B., A.M., Y.H., L.Z., A.I., O.H., and Q.X.), King\u2019s College London British Heart Foundation Centre, London, England; the Department of Vascular Biology (Y.S.), Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan; the Bywaters Centre for Vascular Inflammation (J.C.M.), Imperial College, Hammersmith Hospital, London, England."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanhua","family":"Hu","sequence":"additional","affiliation":[{"name":"From the Department of Physiology (X.B. and X.W.), Peking University Health Science Center, Beijing, China; the Cardiovascular Division (X.B., A.M., Y.H., L.Z., A.I., O.H., and Q.X.), King\u2019s College London British Heart Foundation Centre, London, England; the Department of Vascular Biology (Y.S.), Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan; the Bywaters Centre for Vascular Inflammation (J.C.M.), Imperial College, Hammersmith Hospital, London, England."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasufumi","family":"Sato","sequence":"additional","affiliation":[{"name":"From the Department of Physiology (X.B. and X.W.), Peking University Health Science Center, Beijing, China; the Cardiovascular Division (X.B., A.M., Y.H., L.Z., A.I., O.H., and Q.X.), King\u2019s College London British Heart Foundation Centre, London, England; the Department of Vascular Biology (Y.S.), Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan; the Bywaters Centre for Vascular Inflammation (J.C.M.), Imperial College, Hammersmith Hospital, London, England."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lingfang","family":"Zeng","sequence":"additional","affiliation":[{"name":"From the Department of Physiology (X.B. and X.W.), Peking University Health Science Center, Beijing, China; the Cardiovascular Division (X.B., A.M., Y.H., L.Z., A.I., O.H., and Q.X.), King\u2019s College London British Heart Foundation Centre, London, England; the Department of Vascular Biology (Y.S.), Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan; the Bywaters Centre for Vascular Inflammation (J.C.M.), Imperial College, Hammersmith Hospital, London, England."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aleksandar","family":"Ivetic","sequence":"additional","affiliation":[{"name":"From the Department of Physiology (X.B. and X.W.), Peking University Health Science Center, Beijing, China; the Cardiovascular Division (X.B., A.M., Y.H., L.Z., A.I., O.H., and Q.X.), King\u2019s College London British Heart Foundation Centre, London, England; the Department of Vascular Biology (Y.S.), Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan; the Bywaters Centre for Vascular Inflammation (J.C.M.), Imperial College, Hammersmith Hospital, London, England."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ouassila","family":"Habi","sequence":"additional","affiliation":[{"name":"From the Department of Physiology (X.B. and X.W.), Peking University Health Science Center, Beijing, China; the Cardiovascular Division (X.B., A.M., Y.H., L.Z., A.I., O.H., and Q.X.), King\u2019s College London British Heart Foundation Centre, London, England; the Department of Vascular Biology (Y.S.), Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan; the Bywaters Centre for Vascular Inflammation (J.C.M.), Imperial College, Hammersmith Hospital, London, England."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Justin C.","family":"Mason","sequence":"additional","affiliation":[{"name":"From the Department of Physiology (X.B. and X.W.), Peking University Health Science Center, Beijing, China; the Cardiovascular Division (X.B., A.M., Y.H., L.Z., A.I., O.H., and Q.X.), King\u2019s College London British Heart Foundation Centre, London, England; the Department of Vascular Biology (Y.S.), Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan; the Bywaters Centre for Vascular Inflammation (J.C.M.), Imperial College, Hammersmith Hospital, London, England."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xian","family":"Wang","sequence":"additional","affiliation":[{"name":"From the Department of Physiology (X.B. and X.W.), Peking University Health Science Center, Beijing, China; the Cardiovascular Division (X.B., A.M., Y.H., L.Z., A.I., O.H., and Q.X.), King\u2019s College London British Heart Foundation Centre, London, England; the Department of Vascular Biology (Y.S.), Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan; the Bywaters Centre for Vascular Inflammation (J.C.M.), Imperial College, Hammersmith Hospital, London, England."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qingbo","family":"Xu","sequence":"additional","affiliation":[{"name":"From the Department of Physiology (X.B. and X.W.), Peking University Health Science Center, Beijing, China; the Cardiovascular Division (X.B., A.M., Y.H., L.Z., A.I., O.H., and Q.X.), King\u2019s College London British Heart Foundation Centre, London, England; the Department of Vascular Biology (Y.S.), Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan; the Bywaters Centre for Vascular Inflammation (J.C.M.), Imperial College, Hammersmith Hospital, London, England."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(99)00377-6"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/res.77.3.445"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198602203140806"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M011317200"},{"key":"e_1_3_3_5_2","doi-asserted-by":"crossref","first-page":"L429","DOI":"10.1152\/ajplung.2000.279.3.L429","volume":"279","year":"2000","unstructured":"Dempsey EC, Newton AC, Mochly-Rosen D, Fields AP, Reyland ME, Insel PA, Messing RO. 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