{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T16:52:38Z","timestamp":1792083158385,"version":"4.4.0"},"reference-count":29,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"19","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2009,11,10]]},"abstract":"<jats:p>\n                    <jats:bold>\n                      <jats:italic>Background\u2014<\/jats:italic>\n                    <\/jats:bold>\n                    Hyperhomocysteinemia (HHcy) is an independent risk factor for cardiovascular disease. Monocytes display inflammatory and resident subsets and commit to specific functions in atherogenesis. In this study, we examined the hypothesis that HHcy modulates monocyte heterogeneity and leads to atherosclerosis.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>\n                      <jats:italic>Methods and Results\u2014<\/jats:italic>\n                    <\/jats:bold>\n                    We established a novel atherosclerosis-susceptible mouse model with both severe HHcy and hypercholesterolemia in which the mouse cystathionine \u03b2-synthase (CBS) and apolipoprotein E (apoE) genes are deficient and an inducible human CBS transgene is introduced to circumvent the neonatal lethality of the CBS deficiency (\n                    <jats:italic>\n                      Tg-hCBS apoE\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      Cbs\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    mice). Severe HHcy accelerated atherosclerosis and inflammatory monocyte\/macrophage accumulation in lesions and increased plasma tumor necrosis factor-\u03b1 and monocyte chemoattractant protein-1 levels in\n                    <jats:italic>\n                      Tg-hCBS apoE\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      Cbs\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    mice fed a high-fat diet. Furthermore, we characterized monocyte heterogeneity in\n                    <jats:italic>\n                      Tg-hCBS apoE\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      Cbs\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    mice and another severe HHcy mouse model (\n                    <jats:italic>\n                      Tg-S466L Cbs\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    ) with a disease-relevant mutation (\n                    <jats:italic>Tg-S466L<\/jats:italic>\n                    ) that lacks hyperlipidemia. HHcy increased monocyte population and selective expansion of inflammatory Ly-6C\n                    <jats:sup>hi<\/jats:sup>\n                    and Ly-6C\n                    <jats:sup>mid<\/jats:sup>\n                    monocyte subsets in blood, spleen, and bone marrow of\n                    <jats:italic>\n                      Tg-S466L Cbs\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    and\n                    <jats:italic>\n                      Tg-hCBS apoE\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      Cbs\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    mice. These changes were exacerbated in\n                    <jats:italic>\n                      Tg-S466L Cbs\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    mice with aging. Addition of\n                    <jats:sc>l<\/jats:sc>\n                    -homocysteine (100 to 500 \u03bcmol\/L), but not\n                    <jats:sc>l<\/jats:sc>\n                    -cysteine, maintained the Ly-6C\n                    <jats:sup>hi<\/jats:sup>\n                    subset and induced the Ly-6C\n                    <jats:sup>mid<\/jats:sup>\n                    subset in cultured mouse primary splenocytes. Homocysteine-induced differentiation of the Ly-6C\n                    <jats:sup>mid<\/jats:sup>\n                    subset was prevented by catalase plus superoxide dismutase and the NAD(P)H oxidase inhibitor apocynin.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>\n                      <jats:italic>Conclusion\u2014<\/jats:italic>\n                    <\/jats:bold>\n                    HHcy promotes differentiation of inflammatory monocyte subsets and their accumulation in atherosclerotic lesions via NAD(P)H oxidase\u2013mediated oxidant stress.\n                  <\/jats:p>","DOI":"10.1161\/circulationaha.109.866889","type":"journal-article","created":{"date-parts":[[2009,10,26]],"date-time":"2009-10-26T21:46:49Z","timestamp":1256593609000},"page":"1893-1902","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":124,"title":["Hyperhomocysteinemia Promotes Inflammatory Monocyte Generation and Accelerates Atherosclerosis in Transgenic Cystathionine \u03b2-Synthase\u2013Deficient Mice"],"prefix":"10.1161","volume":"120","author":[{"given":"Daqing","family":"Zhang","sequence":"first","affiliation":[{"name":"From the Department of Pharmacology, Cardiovascular Research Center, and Sol Sherry Thrombosis Research Center, Temple University School of Medicine, Philadelphia, Pa (D.Z., X.J., P.F., Y.Y., J.S., X.Y., H.W.); Department of Cardiology, Shengjing Hospital of China Medical University, Shenyang, People\u2019s Republic of China (D.Z.); Division of Population Science, Fox Chase Cancer Center, Philadelphia, Pa (S.G, W.D.K.); Department of Medicine, Weill Cornell Medical College, New York, NY (A.I.S.); and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohua","family":"Jiang","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology, Cardiovascular Research Center, and Sol Sherry Thrombosis Research Center, Temple University School of Medicine, Philadelphia, Pa (D.Z., X.J., P.F., Y.Y., J.S., X.Y., H.W.); Department of Cardiology, Shengjing Hospital of China Medical University, Shenyang, People\u2019s Republic of China (D.Z.); Division of Population Science, Fox Chase Cancer Center, Philadelphia, Pa (S.G, W.D.K.); Department of Medicine, Weill Cornell Medical College, New York, NY (A.I.S.); and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pu","family":"Fang","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology, Cardiovascular Research Center, and Sol Sherry Thrombosis Research Center, Temple University School of Medicine, Philadelphia, Pa (D.Z., X.J., P.F., Y.Y., J.S., X.Y., H.W.); Department of Cardiology, Shengjing Hospital of China Medical University, Shenyang, People\u2019s Republic of China (D.Z.); Division of Population Science, Fox Chase Cancer Center, Philadelphia, Pa (S.G, W.D.K.); Department of Medicine, Weill Cornell Medical College, New York, NY (A.I.S.); and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Yan","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology, Cardiovascular Research Center, and Sol Sherry Thrombosis Research Center, Temple University School of Medicine, Philadelphia, Pa (D.Z., X.J., P.F., Y.Y., J.S., X.Y., H.W.); Department of Cardiology, Shengjing Hospital of China Medical University, Shenyang, People\u2019s Republic of China (D.Z.); Division of Population Science, Fox Chase Cancer Center, Philadelphia, Pa (S.G, W.D.K.); Department of Medicine, Weill Cornell Medical College, New York, NY (A.I.S.); and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Song","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology, Cardiovascular Research Center, and Sol Sherry Thrombosis Research Center, Temple University School of Medicine, Philadelphia, Pa (D.Z., X.J., P.F., Y.Y., J.S., X.Y., H.W.); Department of Cardiology, Shengjing Hospital of China Medical University, Shenyang, People\u2019s Republic of China (D.Z.); Division of Population Science, Fox Chase Cancer Center, Philadelphia, Pa (S.G, W.D.K.); Department of Medicine, Weill Cornell Medical College, New York, NY (A.I.S.); and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sapna","family":"Gupta","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology, Cardiovascular Research Center, and Sol Sherry Thrombosis Research Center, Temple University School of Medicine, Philadelphia, Pa (D.Z., X.J., P.F., Y.Y., J.S., X.Y., H.W.); Department of Cardiology, Shengjing Hospital of China Medical University, Shenyang, People\u2019s Republic of China (D.Z.); Division of Population Science, Fox Chase Cancer Center, Philadelphia, Pa (S.G, W.D.K.); Department of Medicine, Weill Cornell Medical College, New York, NY (A.I.S.); and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew I.","family":"Schafer","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology, Cardiovascular Research Center, and Sol Sherry Thrombosis Research Center, Temple University School of Medicine, Philadelphia, Pa (D.Z., X.J., P.F., Y.Y., J.S., X.Y., H.W.); Department of Cardiology, Shengjing Hospital of China Medical University, Shenyang, People\u2019s Republic of China (D.Z.); Division of Population Science, Fox Chase Cancer Center, Philadelphia, Pa (S.G, W.D.K.); Department of Medicine, Weill Cornell Medical College, New York, NY (A.I.S.); and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Durante","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology, Cardiovascular Research Center, and Sol Sherry Thrombosis Research Center, Temple University School of Medicine, Philadelphia, Pa (D.Z., X.J., P.F., Y.Y., J.S., X.Y., H.W.); Department of Cardiology, Shengjing Hospital of China Medical University, Shenyang, People\u2019s Republic of China (D.Z.); Division of Population Science, Fox Chase Cancer Center, Philadelphia, Pa (S.G, W.D.K.); Department of Medicine, Weill Cornell Medical College, New York, NY (A.I.S.); and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Warren D.","family":"Kruger","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology, Cardiovascular Research Center, and Sol Sherry Thrombosis Research Center, Temple University School of Medicine, Philadelphia, Pa (D.Z., X.J., P.F., Y.Y., J.S., X.Y., H.W.); Department of Cardiology, Shengjing Hospital of China Medical University, Shenyang, People\u2019s Republic of China (D.Z.); Division of Population Science, Fox Chase Cancer Center, Philadelphia, Pa (S.G, W.D.K.); Department of Medicine, Weill Cornell Medical College, New York, NY (A.I.S.); and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofeng","family":"Yang","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology, Cardiovascular Research Center, and Sol Sherry Thrombosis Research Center, Temple University School of Medicine, Philadelphia, Pa (D.Z., X.J., P.F., Y.Y., J.S., X.Y., H.W.); Department of Cardiology, Shengjing Hospital of China Medical University, Shenyang, People\u2019s Republic of China (D.Z.); Division of Population Science, Fox Chase Cancer Center, Philadelphia, Pa (S.G, W.D.K.); Department of Medicine, Weill Cornell Medical College, New York, NY (A.I.S.); and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Wang","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology, Cardiovascular Research Center, and Sol Sherry Thrombosis Research Center, Temple University School of Medicine, Philadelphia, Pa (D.Z., X.J., P.F., Y.Y., J.S., X.Y., H.W.); Department of Cardiology, Shengjing Hospital of China Medical University, Shenyang, People\u2019s Republic of China (D.Z.); Division of Population Science, Fox Chase Cancer Center, Philadelphia, Pa (S.G, W.D.K.); Department of Medicine, Weill Cornell Medical College, New York, NY (A.I.S.); and..."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199603213341203"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199707243370403"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1995.03530130055028"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ddmec.2005.05.029"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118383"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.40.25380"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V99.3.939.h80302000939_939_945"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2005.08.016"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.atv.0000189559.87328.e4"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1161\/atvbaha.107.148544"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.res.0000242559.42077.22"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/136.6.1741S"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI29950"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri1733"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0037-1613862"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.5.1585"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-08-2606"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.res.0000129182.46440.4a"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20773"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-06-096701"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M603656200"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830181125"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni1309"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.08-120584"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddi224"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.103.22.2717"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20032152"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2008.10.030"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20051810"}],"container-title":["Circulation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/CIRCULATIONAHA.109.866889","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T02:17:06Z","timestamp":1715566626000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/CIRCULATIONAHA.109.866889"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,11,10]]},"references-count":29,"journal-issue":{"issue":"19","published-print":{"date-parts":[[2009,11,10]]}},"alternative-id":["10.1161\/CIRCULATIONAHA.109.866889"],"URL":"https:\/\/doi.org\/10.1161\/circulationaha.109.866889","relation":{},"ISSN":["0009-7322","1524-4539"],"issn-type":[{"value":"0009-7322","type":"print"},{"value":"1524-4539","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,11,10]]},"assertion":[{"value":"2009-10-26","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}