{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T07:27:34Z","timestamp":1780990054986,"version":"3.54.1"},"reference-count":46,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2009,10,9]]},"abstract":"<jats:p>\n            <jats:bold>\n              <jats:italic>\n                <jats:underline>Rationale<\/jats:underline>\n                :\n              <\/jats:italic>\n            <\/jats:bold>\n            Hyperhomocysteinemia contributes to vascular dysfunction and risks of cardiovascular diseases. Stromal cell\u2013derived factor (SDF)-1, a chemokine expressed by endothelial cells (ECs), is highly expressed in advanced atherosclerotic lesions. The interplays among homocysteine, chemokines, and shear stress in regulating vascular endothelial function are not clearly understood.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>\n                <jats:underline>Objective<\/jats:underline>\n                :\n              <\/jats:italic>\n            <\/jats:bold>\n            To investigate the mechanisms for modulations of EC SDF-1 expression by homocysteine and shear stress.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>\n                <jats:underline>Methods and Results<\/jats:underline>\n                :\n              <\/jats:italic>\n            <\/jats:bold>\n            Homocysteine stimulation induced dose- and time-dependent SDF-1 expression and phosphorylation of mitogen-activated protein kinases extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38. By using specific inhibitors, small interfering (si)RNA, and dominant negative mutants, we demonstrated that activation of JNK pathway is critical for the homocysteine-induced SDF-1 expression. Transcription factor ELISA and chromatin immunoprecipitation assays showed that homocysteine increased Sp1- and AP-1\u2013DNA binding activities in ECs. Inhibition of Sp1 and AP-1 activations by specific siRNA blocked the homocysteine-induced SDF-1 promoter activity and expression. Preshearing of ECs for 1 to 4 hours at 20 dyn\/cm\n            <jats:sup>2<\/jats:sup>\n            inhibited the homocysteine-induced JNK phosphorylation, Sp1 and AP-1 activation, and SDF-1 expression. The homocysteine-induced SDF-1 expression was suppressed by NO donor. Inhibitor or siRNA for endothelial NO synthase abolished the shear inhibition of SDF-1 expression.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>\n                <jats:underline>Conclusions<\/jats:underline>\n                :\n              <\/jats:italic>\n            <\/jats:bold>\n            Our findings serve to elucidate the molecular mechanisms underlying the homocysteine induction of SDF-1 expression in ECs and the shear stress protection against this induction.\n          <\/jats:p>","DOI":"10.1161\/circresaha.109.206524","type":"journal-article","created":{"date-parts":[[2009,9,11]],"date-time":"2009-09-11T01:44:56Z","timestamp":1252633496000},"page":"755-763","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":29,"title":["Shear Stress Inhibits Homocysteine-Induced Stromal Cell\u2013Derived Factor-1 Expression in Endothelial Cells"],"prefix":"10.1161","volume":"105","author":[{"given":"Mao-Lin","family":"Sung","sequence":"first","affiliation":[{"name":"From the Department of Cardiology (M.-L.S., C.-K.Y.), St Martin De Porres Hospital, Chiayi, Taiwan; Department of Medical Laboratory Science and Biotechnology (M.-L.S., J.-C.C.), China Medical University, Taichung, Taiwan; Department of Cell Biology and Anatomy (C.-C.W.), School of Medicine, National Cheng Kung University, Tainan, Taiwan; Department of Biochemical Science and Technology (H.-I.C., C.-N.C.), National Chiayi University, Taiwan; Nursing Department (H.J.C.), Chung Jen College of Nursing,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chia-Ching","family":"Wu","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology (M.-L.S., C.-K.Y.), St Martin De Porres Hospital, Chiayi, Taiwan; Department of Medical Laboratory Science and Biotechnology (M.-L.S., J.-C.C.), China Medical University, Taichung, Taiwan; Department of Cell Biology and Anatomy (C.-C.W.), School of Medicine, National Cheng Kung University, Tainan, Taiwan; Department of Biochemical Science and Technology (H.-I.C., C.-N.C.), National Chiayi University, Taiwan; Nursing Department (H.J.C.), Chung Jen College of Nursing,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsin-I","family":"Chang","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology (M.-L.S., C.-K.Y.), St Martin De Porres Hospital, Chiayi, Taiwan; Department of Medical Laboratory Science and Biotechnology (M.-L.S., J.-C.C.), China Medical University, Taichung, Taiwan; Department of Cell Biology and Anatomy (C.-C.W.), School of Medicine, National Cheng Kung University, Tainan, Taiwan; Department of Biochemical Science and Technology (H.-I.C., C.-N.C.), National Chiayi University, Taiwan; Nursing Department (H.J.C.), Chung Jen College of Nursing,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chia-Kuang","family":"Yen","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology (M.-L.S., C.-K.Y.), St Martin De Porres Hospital, Chiayi, Taiwan; Department of Medical Laboratory Science and Biotechnology (M.-L.S., J.-C.C.), China Medical University, Taichung, Taiwan; Department of Cell Biology and Anatomy (C.-C.W.), School of Medicine, National Cheng Kung University, Tainan, Taiwan; Department of Biochemical Science and Technology (H.-I.C., C.-N.C.), National Chiayi University, Taiwan; Nursing Department (H.J.C.), Chung Jen College of Nursing,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heng Jung","family":"Chen","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology (M.-L.S., C.-K.Y.), St Martin De Porres Hospital, Chiayi, Taiwan; Department of Medical Laboratory Science and Biotechnology (M.-L.S., J.-C.C.), China Medical University, Taichung, Taiwan; Department of Cell Biology and Anatomy (C.-C.W.), School of Medicine, National Cheng Kung University, Tainan, Taiwan; Department of Biochemical Science and Technology (H.-I.C., C.-N.C.), National Chiayi University, Taiwan; Nursing Department (H.J.C.), Chung Jen College of Nursing,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ju-Chien","family":"Cheng","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology (M.-L.S., C.-K.Y.), St Martin De Porres Hospital, Chiayi, Taiwan; Department of Medical Laboratory Science and Biotechnology (M.-L.S., J.-C.C.), China Medical University, Taichung, Taiwan; Department of Cell Biology and Anatomy (C.-C.W.), School of Medicine, National Cheng Kung University, Tainan, Taiwan; Department of Biochemical Science and Technology (H.-I.C., C.-N.C.), National Chiayi University, Taiwan; Nursing Department (H.J.C.), Chung Jen College of Nursing,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu","family":"Chien","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology (M.-L.S., C.-K.Y.), St Martin De Porres Hospital, Chiayi, Taiwan; Department of Medical Laboratory Science and Biotechnology (M.-L.S., J.-C.C.), China Medical University, Taichung, Taiwan; Department of Cell Biology and Anatomy (C.-C.W.), School of Medicine, National Cheng Kung University, Tainan, Taiwan; Department of Biochemical Science and Technology (H.-I.C., C.-N.C.), National Chiayi University, Taiwan; Nursing Department (H.J.C.), Chung Jen College of Nursing,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng-Nan","family":"Chen","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology (M.-L.S., C.-K.Y.), St Martin De Porres Hospital, Chiayi, Taiwan; Department of Medical Laboratory Science and Biotechnology (M.-L.S., J.-C.C.), China Medical University, Taichung, Taiwan; Department of Cell Biology and Anatomy (C.-C.W.), School of Medicine, National Cheng Kung University, Tainan, Taiwan; Department of Biochemical Science and Technology (H.-I.C., C.-N.C.), National Chiayi University, Taiwan; Nursing Department (H.J.C.), Chung Jen College of 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