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We investigated the hypothesis that cardiac secretion of a unique phospholipase A\n              <jats:sub>2<\/jats:sub>\n              recently identified by our laboratory (cardiac secreted phospholipase A\n              <jats:sub>2<\/jats:sub>\n              [\n              <jats:styled-content style=\"fixed-case\">sPLA<\/jats:styled-content>\n              <jats:sub>2<\/jats:sub>\n              ]) establishes a heart\u2013liver endocrine axis that is negatively regulated by matrix metalloproteinase\u20102 (MMP\u20102).\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              In\n              <jats:italic>Mmp2<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              mice, cardiac (but not hepatic)\n              <jats:styled-content style=\"fixed-case\">sPLA<\/jats:styled-content>\n              <jats:sub>2<\/jats:sub>\n              was elevated, leading to hepatic inflammation, immune cell infiltration, dysregulation of the sterol regulatory element binding protein\u20102 and liver X receptor\u2010\u03b1 pathways, abnormal transcriptional responses to dietary cholesterol, and elevated triglycerides in very low\u2010density lipoprotein and in the liver. Expression of monocyte chemoattractant protein\u20103, a known MMP\u20102 substrate, was elevated at both\n              <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content>\n              and protein levels in the heart. Functional studies including in\u00a0vivo antibody neutralization identified cardiac monocyte chemoattractant protein 3 as a possible agonist of cardiac\n              <jats:styled-content style=\"fixed-case\">sPLA<\/jats:styled-content>\n              <jats:sub>2<\/jats:sub>\n              secretion. Conversely, systemic\n              <jats:styled-content style=\"fixed-case\">sPLA<\/jats:styled-content>\n              <jats:sub>2<\/jats:sub>\n              inhibition almost fully normalized the cardiohepatic phenotype without affecting monocyte chemoattractant protein\u20103. Finally, wild\u2010type mice that received h\n              <jats:styled-content style=\"fixed-case\">igh\u2010performance liquid chromatography<\/jats:styled-content>\n              \u2013isolated cardiac\n              <jats:styled-content style=\"fixed-case\">sPLA<\/jats:styled-content>\n              <jats:sub>2<\/jats:sub>\n              from\n              <jats:italic>Mmp2<\/jats:italic>\n              <jats:sup>\n                <jats:italic>\u2212\/\u2212<\/jats:italic>\n              <\/jats:sup>\n              donors developed a cardiohepatic gene expression profile similar to that of\n              <jats:italic>Mmp2<\/jats:italic>\n              <jats:sup>\n                <jats:italic>\u2212\/\u2212<\/jats:italic>\n              <\/jats:sup>\n              mice.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              These findings identified the novel MMP\u20102\/cardiac\n              <jats:styled-content style=\"fixed-case\">sPLA<\/jats:styled-content>\n              <jats:sub>2<\/jats:sub>\n              pathway that endows the heart with important endocrine functions, including regulation of inflammation and lipid metabolism in the liver. Our findings could also help explain how\n              <jats:italic>\n                <jats:styled-content style=\"fixed-case\">MMP<\/jats:styled-content>\n                2\n              <\/jats:italic>\n              deficiency leads to cardiac problems, inflammation, and metabolic dysregulation in patients.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.115.002553","type":"journal-article","created":{"date-parts":[[2015,11,14]],"date-time":"2015-11-14T02:43:37Z","timestamp":1447469017000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":39,"title":["Identification of a Novel Heart\u2013Liver Axis: Matrix Metalloproteinase\u20102 Negatively Regulates Cardiac Secreted Phospholipase A\n            <sub>2<\/sub>\n            to Modulate Lipid Metabolism and Inflammation in the Liver"],"prefix":"10.1161","volume":"4","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":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evan","family":"Berry","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vesna","family":"Brglez","sequence":"additional","affiliation":[{"name":"Institut de Pharmacologie Mol\u00e9culaire et Cellulaire, Centre National de la Recherche Scientifique, Universit\u00e9 de Nice\u2010Sophia Antipolis, Valbonne, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dickson","family":"Leung","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tae Jin","family":"Yun","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular Physiology and Immunology, Institut de Recherches Cliniques de Montr\u00e9al, Montr\u00e9al, Qu\u00e9bec, Canada"},{"name":"Division of Experimental Medicine, Department of Medicine, McGill University, Montreal, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun Seong","family":"Lee","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular Physiology and Immunology, Institut de Recherches Cliniques de Montr\u00e9al, Montr\u00e9al, Qu\u00e9bec, Canada"},{"name":"Department of Microbiology and Immunology, University of Montreal, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janos G.","family":"Filep","sequence":"additional","affiliation":[{"name":"Innate Immunity System (Inflammation) and 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