{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T08:36:12Z","timestamp":1779179772799,"version":"3.51.4"},"reference-count":58,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"12","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2016,12]]},"abstract":"<jats:sec id=\"jah31926-sec-0001\" xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              <jats:styled-content style=\"fixed-case\" toggle=\"no\">NK<\/jats:styled-content>\n              2 homeobox 5 (Nkx2\u20105) is a cardiac homeobox transcription factor that is expressed in a broad range of cardiac sublineages. Embryos lacking Nkx2\u20105 are nonviable attributed to growth retardation and gross abnormalities of the heart. However, the role of Nkx2\u20105 in atherosclerosis remains elusive. This study aims to elucidate the specific functions of Nkx2\u20105 during atherogenesis and in established atherosclerotic plaques.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec id=\"jah31926-sec-0002\" xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              Two types of atherosclerotic lesions were created in ApoE\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              mice through 2 different dietary manipulations. Mice fed a standard chow diet were sacrificed at 20 weeks old, a time point at which mice developed early\u2010stage atherosclerotic lesions. The other half of mice were fed a western diet from 6 to 22 weeks old and then sacrificed. These mice demonstrated advanced atherosclerosis. No Nkx2\u20105 was detected in normal arteries; however, it was abundantly present in the intima of atherosclerotic lesions and localized in macrophages and smooth muscle cells. Adenovirus gene transfer of Nkx2\u20105 markedly ameliorated and stabilized the atherosclerotic plaques, and knockdown of Nkx2\u20105 significantly exacerbated the disease. Molecular studies indicated that expression of specific members of matrix metalloproteinases and tissue inhibitor of metalloproteinases, which play a crucial role in the progression of atherosclerosis, were directly regulated by Nkx2\u20105. Furthermore, we demonstrated that the compromised endothelial function, which was considered as a hallmark of early atherosclerosis, could be improved by Nkx2\u20105 gene transfer.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec id=\"jah31926-sec-0003\" xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">Nkx2\u20105 exerts antiatherogenic effects, which may partly be attributed to regulation on matrix metalloproteinases and tissue inhibitor of metalloproteinases, thus\u00a0stabilizing atherosclerotic plaque; besides, it improves endothelial function by inhibiting leukocyte adhesion to the endothelium.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.116.004440","type":"journal-article","created":{"date-parts":[[2016,12,20]],"date-time":"2016-12-20T01:55:56Z","timestamp":1482198956000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":9,"title":["Nkx2\u20105 Is Expressed in Atherosclerotic Plaques and Attenuates Development of Atherosclerosis in Apolipoprotein E\u2013Deficient Mice"],"prefix":"10.1161","volume":"5","author":[{"given":"Meng","family":"Du","sequence":"first","affiliation":[{"name":"Huazhong University of Science and Technology","place":["Wuhan, China"]},{"name":"Huazhong University of Science and Technology","place":["Wuhan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaojing","family":"Wang","sequence":"additional","affiliation":[{"name":"Huazhong University of Science and Technology","place":["Wuhan, China"]},{"name":"Huazhong University of Science and Technology","place":["Wuhan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin","family":"Tan","sequence":"additional","affiliation":[{"name":"Huazhong University of Science and Technology","place":["Wuhan, China"]},{"name":"Huazhong University of Science and Technology","place":["Wuhan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiangrao","family":"Li","sequence":"additional","affiliation":[{"name":"Huazhong University of Science and Technology","place":["Wuhan, China"]},{"name":"Huazhong University of Science and Technology","place":["Wuhan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dandan","family":"Huang","sequence":"additional","affiliation":[{"name":"Huazhong University of Science and Technology","place":["Wuhan, China"]},{"name":"Huazhong University of Science and Technology","place":["Wuhan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kun","family":"Huang","sequence":"additional","affiliation":[{"name":"Huazhong University of Science and Technology","place":["Wuhan, China"]},{"name":"Huazhong University of Science and Technology","place":["Wuhan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liu","family":"Yang","sequence":"additional","affiliation":[{"name":"Huazhong University of Science and Technology","place":["Wuhan, China"]},{"name":"Huazhong University of Science and Technology","place":["Wuhan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fengxiao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Huazhong University of Science and Technology","place":["Wuhan, China"]},{"name":"Huazhong University of Science and Technology","place":["Wuhan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Wang","sequence":"additional","affiliation":[{"name":"Huazhong University of Science and Technology","place":["Wuhan, China"]},{"name":"Huazhong University of Science and Technology","place":["Wuhan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dan","family":"Huang","sequence":"additional","affiliation":[{"name":"Huazhong University of Science and Technology","place":["Wuhan, China"]},{"name":"Huazhong University of Science and Technology","place":["Wuhan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kai","family":"Huang","sequence":"additional","affiliation":[{"name":"Huazhong University of Science and Technology","place":["Wuhan, China"]},{"name":"Huazhong University of Science and Technology","place":["Wuhan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1016\/j.cell.2007.01.042","article-title":"An Nkx2\u20105\/Bmp2\/Smad1 negative feedback loop controls heart progenitor specification and proliferation","volume":"128","author":"Prall OW","year":"2007","unstructured":"Prall OW, Menon MK, Solloway MJ, Watanabe Y, Zaffran S, Bajolle F, Biben C, McBride JJ, Robertson BR, Chaulet H, Stennard FA, Wise N, Schaft D, Wolstein O, Furtado MB, Shiratori H, Chien KR, Hamada H, Black BL, Saga Y, Robertson EJ, Buckingham ME, Harvey RP. 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