{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T09:26:07Z","timestamp":1768814767860,"version":"3.49.0"},"reference-count":85,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"10","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2016,10,3]]},"abstract":"\n Background<\/jats:title>\n \n The development of atherosclerosis is strongly linked to disorders of cholesterol metabolism. Matrix metalloproteinases (\n MMP<\/jats:styled-content>\n s) are dysregulated in patients and animal models with atherosclerosis. Whether systemic\n MMP<\/jats:styled-content>\n activity influences cholesterol metabolism is unknown.\n <\/jats:p>\n <\/jats:sec>\n \n Methods and Results<\/jats:title>\n \n We examined\n MMP<\/jats:styled-content>\n \u20109\u2013deficient (\n Mmp9<\/jats:italic>\n \n \u2212\/\u2212<\/jats:italic>\n <\/jats:sup>\n ) mice and found them to have abnormal lipid gene transcriptional responses to dietary cholesterol supplementation. As opposed to\n Mmp9<\/jats:italic>\n \n +\/+<\/jats:italic>\n <\/jats:sup>\n (wild\u2010type) mice,\n Mmp9<\/jats:italic>\n \n \u2212\/\u2212<\/jats:italic>\n <\/jats:sup>\n mice failed to decrease the hepatic expression of sterol regulatory element binding protein 2 pathway genes, which control hepatic cholesterol biosynthesis and uptake. Furthermore,\n Mmp9<\/jats:italic>\n \n \u2212\/\u2212<\/jats:italic>\n <\/jats:sup>\n mice failed to increase the expression of genes encoding the rate\u2010limiting enzymes in biliary cholesterol excretion (eg,\n Cyp7a<\/jats:italic>\n and\n Cyp27a<\/jats:italic>\n ). In contrast,\n MMP<\/jats:styled-content>\n \u20109 deficiency did not impair intestinal cholesterol absorption, as shown by the\n 14<\/jats:sup>\n C\u2010cholesterol and\n 3<\/jats:sup>\n H\u2010sitostanol absorption assay. Similar to our earlier study on\n Mmp2<\/jats:italic>\n \n \u2212\/\u2212<\/jats:italic>\n <\/jats:sup>\n mice, we observed that\n Mmp9<\/jats:italic>\n \n \u2212\/\u2212<\/jats:italic>\n <\/jats:sup>\n mice had elevated plasma secreted phospholipase A\n 2<\/jats:sub>\n activity. Pharmacological inhibition of systemic circulating secreted phospholipase A\n 2<\/jats:sub>\n activity (with varespladib) partially normalized the hepatic transcriptional responses to dietary cholesterol in\n Mmp9<\/jats:italic>\n \n \u2212\/\u2212<\/jats:italic>\n <\/jats:sup>\n mice. Functional studies with mice deficient in other\n MMP<\/jats:styled-content>\n s suggested an important role for the\n MMP<\/jats:styled-content>\n system, as a whole, in modulation of cholesterol metabolism.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Our results show that\n MMP<\/jats:styled-content>\n \u20109 modulates cholesterol metabolism, at least in part, through a novel\n MMP<\/jats:styled-content>\n \u20109\u2013plasma secreted phospholipase A\n 2<\/jats:sub>\n axis that affects the hepatic transcriptional responses to dietary cholesterol. Furthermore, the data suggest that dysregulation of the\n MMP<\/jats:styled-content>\n system can result in metabolic disorder, which could lead to atherosclerosis and coronary heart disease.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/jaha.116.004228","type":"journal-article","created":{"date-parts":[[2016,10,1]],"date-time":"2016-10-01T02:39:52Z","timestamp":1475289592000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":30,"title":["Novel Role for Matrix Metalloproteinase 9 in Modulation of Cholesterol Metabolism"],"prefix":"10.1161","volume":"5","author":[{"given":"Samuel","family":"Hernandez\u2010Anzaldo","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vesna","family":"Brglez","sequence":"additional","affiliation":[{"name":"Institut de Pharmacologie Mol\u00e9culaire et Cellulaire, Centre National de la Recherche Scientifique, Universit\u00e9 C\u00f4te d'Azur, Nice, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bianca","family":"Hemmeryckx","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Sciences, Center for Molecular and Vascular Biology, KU Leuven, Leuven, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dickson","family":"Leung","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janos G.","family":"Filep","sequence":"additional","affiliation":[{"name":"The Maisonneuve\u2010Rosemont Hospital Research Centre, University of Montreal, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean E.","family":"Vance","sequence":"additional","affiliation":[{"name":"Department of Medicine, Cardiovascular Research Group, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dennis E.","family":"Vance","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zamaneh","family":"Kassiri","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada"},{"name":"Mazankowski Alberta Heart Institute, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roger H.","family":"Lijnen","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Sciences, Center for Molecular and Vascular Biology, KU Leuven, Leuven, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G\u00e9rard","family":"Lambeau","sequence":"additional","affiliation":[{"name":"Institut de Pharmacologie Mol\u00e9culaire et Cellulaire, Centre National de la Recherche Scientifique, Universit\u00e9 C\u00f4te d'Azur, Nice, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlos","family":"Fernandez\u2010Patron","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada"},{"name":"Mazankowski Alberta Heart Institute, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_6_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2009.09.015"},{"key":"e_1_3_6_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.115.002553"},{"key":"e_1_3_6_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.115.001868"},{"key":"e_1_3_6_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2004.07.010"},{"key":"e_1_3_6_6_2","doi-asserted-by":"publisher","DOI":"10.3109\/1354750X.2013.866165"},{"key":"e_1_3_6_7_2","first-page":"247","article-title":"MMP\u20102 and MMP\u20109 are prominent matrix metalloproteinases during atherosclerosis development in the Ldlr(\u2010\/\u2010)Apob(100\/100) mouse","volume":"28","author":"Wagsater D","year":"2011","unstructured":"Wagsater D, Zhu C, Bjorkegren J, Skogsberg J, Eriksson P. 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