{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T13:30:02Z","timestamp":1765546202779,"version":"3.41.2"},"reference-count":57,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Heart Failure"],"published-print":{"date-parts":[[2017,2]]},"abstract":"<jats:sec>\n            <jats:title>Background\u2014<\/jats:title>\n            <jats:p>Despite increased secondary cardiovascular events in patients with ischemic cardiomyopathy (ICM), the expression of innate cardiac protective molecules in the hearts of patients with ICM is incompletely characterized. Therefore, we used a nonbiased RNAseq approach to determine whether differences in cardiac protective molecules occur with ICM.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods and Results\u2014<\/jats:title>\n            <jats:p>\n              RNAseq analysis of human control and ICM left ventricular samples demonstrated a significant decrease in\n              <jats:italic>KCNJ11<\/jats:italic>\n              expression with ICM.\n              <jats:italic>KCNJ11<\/jats:italic>\n              encodes the Kir6.2 subunit of the cardioprotective K\n              <jats:sub>ATP<\/jats:sub>\n              channel. Using wild-type mice and\n              <jats:italic>kcnj11<\/jats:italic>\n              -deficient (\n              <jats:italic>kcnj11<\/jats:italic>\n              -null) mice, we examined the effect of\n              <jats:italic>kcnj11<\/jats:italic>\n              expression on cardiac function during ischemia-reperfusion injury. Reactive oxygen species generation increased in\n              <jats:italic>kcnj11<\/jats:italic>\n              -null hearts above that found in wild-type mice hearts after ischemia-reperfusion injury. Continuous left ventricular pressure measurement during ischemia and reperfusion demonstrated a more compromised diastolic function in\n              <jats:italic>kcnj11<\/jats:italic>\n              -null compared with wild-type mice during reperfusion. Analysis of key calcium-regulating proteins revealed significant differences in\n              <jats:italic>kcnj11<\/jats:italic>\n              -null mice. Despite impaired relaxation,\n              <jats:italic>kcnj11<\/jats:italic>\n              -null hearts increased phospholamban Ser16 phosphorylation, a modification that results in the dissociation of phospholamban from sarcoendoplasmic reticulum Ca\n              <jats:sup>2+<\/jats:sup>\n              , thereby increasing sarcoendoplasmic reticulum Ca\n              <jats:sup>2+<\/jats:sup>\n              \u2013mediated calcium reuptake. However,\n              <jats:italic>kcnj11<\/jats:italic>\n              -null mice also had increased 3-nitrotyrosine modification of the sarcoendoplasmic reticulum Ca\n              <jats:sup>2+<\/jats:sup>\n              -ATPase, a modification that irreversibly impairs sarcoendoplasmic reticulum Ca\n              <jats:sup>2+<\/jats:sup>\n              function, thereby contributing to diastolic dysfunction.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>\n              <jats:italic>KCNJ11<\/jats:italic>\n              expression is decreased in human ICM. Lack of\n              <jats:italic>kcnj11<\/jats:italic>\n              expression increases peroxynitrite-mediated modification of the key calcium-handling protein sarcoendoplasmic reticulum Ca\n              <jats:sup>2+<\/jats:sup>\n              -ATPase after myocardial ischemia-reperfusion injury, contributing to impaired diastolic function. These data suggest a mechanism for ischemia-induced diastolic dysfunction in patients with ICM.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circheartfailure.116.003523","type":"journal-article","created":{"date-parts":[[2017,2,17]],"date-time":"2017-02-17T02:10:33Z","timestamp":1487297433000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":7,"title":["<i>Kcnj11<\/i>\n            Ablation Is Associated With Increased Nitro-Oxidative Stress During Ischemia-Reperfusion Injury"],"prefix":"10.1161","volume":"10","author":[{"given":"Bo","family":"Zhang","sequence":"first","affiliation":[{"name":"From the Division of Cardiovascular Medicine, Davis Heart and Lung Research Institute (B.Z., D.G.W., Z.X., R.H., H.H., S.V., J.L.Z.), Department of Physiology and Cell Biology (B.Z., J.L.Z., M.J.K., M.T.Z.), The Ohio State University, Columbus; Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, HuBei, China (B.Z.); Department of Biostatistics (Y.S., M.X., F.E.H.), Division of Clinical Pharmacology, Department of Medicine..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatiana","family":"Novitskaya","sequence":"additional","affiliation":[{"name":"From the Division of Cardiovascular Medicine, Davis Heart and Lung Research Institute (B.Z., D.G.W., Z.X., R.H., H.H., S.V., J.L.Z.), Department of Physiology and Cell Biology (B.Z., J.L.Z., M.J.K., M.T.Z.), The Ohio State University, Columbus; Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, HuBei, China (B.Z.); Department of Biostatistics (Y.S., M.X., F.E.H.), Division of Clinical Pharmacology, Department of Medicine..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Debra G.","family":"Wheeler","sequence":"additional","affiliation":[{"name":"From the Division of Cardiovascular Medicine, Davis Heart and Lung Research Institute (B.Z., D.G.W., Z.X., R.H., H.H., S.V., J.L.Z.), Department of Physiology and Cell Biology (B.Z., J.L.Z., M.J.K., M.T.Z.), The Ohio State University, Columbus; Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, HuBei, China (B.Z.); Department of Biostatistics (Y.S., M.X., F.E.H.), Division of Clinical Pharmacology, Department of Medicine..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhaobin","family":"Xu","sequence":"additional","affiliation":[{"name":"From the Division of Cardiovascular Medicine, Davis Heart and Lung Research Institute (B.Z., D.G.W., Z.X., R.H., H.H., S.V., J.L.Z.), Department of Physiology and Cell Biology (B.Z., J.L.Z., M.J.K., M.T.Z.), The Ohio State University, Columbus; Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, HuBei, China (B.Z.); Department of Biostatistics (Y.S., M.X., F.E.H.), Division of Clinical Pharmacology, Department of Medicine..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Chepurko","sequence":"additional","affiliation":[{"name":"From the Division of Cardiovascular Medicine, Davis Heart and Lung Research Institute (B.Z., D.G.W., Z.X., R.H., H.H., S.V., J.L.Z.), Department of Physiology and Cell Biology (B.Z., J.L.Z., M.J.K., M.T.Z.), The Ohio State University, Columbus; Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, HuBei, China (B.Z.); Department of Biostatistics (Y.S., M.X., F.E.H.), Division of Clinical Pharmacology, Department of Medicine..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryan","family":"Huttinger","sequence":"additional","affiliation":[{"name":"From the Division of Cardiovascular Medicine, Davis Heart and Lung Research Institute (B.Z., D.G.W., Z.X., R.H., H.H., S.V., J.L.Z.), Department of Physiology and Cell Biology (B.Z., J.L.Z., M.J.K., M.T.Z.), The Ohio State University, Columbus; Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, HuBei, China (B.Z.); Department of Biostatistics (Y.S., M.X., F.E.H.), Division of Clinical Pharmacology, Department of Medicine..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heng","family":"He","sequence":"additional","affiliation":[{"name":"From the Division of Cardiovascular Medicine, Davis Heart and Lung Research Institute (B.Z., D.G.W., Z.X., R.H., H.H., S.V., J.L.Z.), Department of Physiology and Cell Biology (B.Z., J.L.Z., M.J.K., M.T.Z.), The Ohio State University, Columbus; Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, HuBei, China (B.Z.); Department of Biostatistics (Y.S., M.X., F.E.H.), Division of Clinical Pharmacology, Department of Medicine..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saradhadevi","family":"Varadharaj","sequence":"additional","affiliation":[{"name":"From the Division of Cardiovascular Medicine, Davis Heart and Lung Research Institute (B.Z., D.G.W., Z.X., R.H., H.H., S.V., J.L.Z.), Department of Physiology and Cell Biology (B.Z., J.L.Z., M.J.K., M.T.Z.), The Ohio State University, Columbus; Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, HuBei, China (B.Z.); Department of Biostatistics (Y.S., M.X., F.E.H.), Division of Clinical Pharmacology, Department of Medicine..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jay L.","family":"Zweier","sequence":"additional","affiliation":[{"name":"From the Division of Cardiovascular Medicine, Davis Heart and Lung Research Institute (B.Z., D.G.W., Z.X., R.H., H.H., S.V., J.L.Z.), Department of Physiology and Cell Biology (B.Z., J.L.Z., M.J.K., M.T.Z.), The Ohio State University, Columbus; Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, HuBei, China (B.Z.); Department of Biostatistics (Y.S., M.X., F.E.H.), Division of Clinical Pharmacology, Department of Medicine..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanna","family":"Song","sequence":"additional","affiliation":[{"name":"From the Division of Cardiovascular Medicine, Davis Heart and Lung Research Institute (B.Z., D.G.W., Z.X., R.H., H.H., S.V., J.L.Z.), Department of Physiology and Cell Biology (B.Z., J.L.Z., M.J.K., M.T.Z.), The Ohio State University, Columbus; Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, HuBei, China (B.Z.); Department of Biostatistics (Y.S., M.X., F.E.H.), Division of Clinical Pharmacology, Department of Medicine..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meng","family":"Xu","sequence":"additional","affiliation":[{"name":"From the Division of Cardiovascular Medicine, Davis Heart and Lung Research Institute (B.Z., D.G.W., Z.X., R.H., H.H., S.V., J.L.Z.), Department of Physiology and Cell Biology (B.Z., J.L.Z., M.J.K., M.T.Z.), The Ohio State University, Columbus; Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, HuBei, China (B.Z.); Department of Biostatistics (Y.S., M.X., F.E.H.), Division of Clinical Pharmacology, Department of Medicine..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"Jr","given":"Frank E.","family":"Harrell","sequence":"additional","affiliation":[{"name":"From the Division of Cardiovascular Medicine, Davis Heart and Lung Research Institute (B.Z., D.G.W., Z.X., R.H., H.H., S.V., J.L.Z.), Department of Physiology and Cell Biology (B.Z., J.L.Z., M.J.K., M.T.Z.), The Ohio State University, Columbus; Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, HuBei, China (B.Z.); Department of Biostatistics (Y.S., M.X., F.E.H.), Division of Clinical Pharmacology, Department of Medicine..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan Ru","family":"Su","sequence":"additional","affiliation":[{"name":"From the Division of Cardiovascular Medicine, Davis Heart and Lung Research Institute (B.Z., D.G.W., Z.X., R.H., H.H., S.V., J.L.Z.), Department of Physiology and Cell Biology (B.Z., J.L.Z., M.J.K., M.T.Z.), The Ohio State University, Columbus; Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, HuBei, China (B.Z.); Department of Biostatistics (Y.S., M.X., F.E.H.), Division of Clinical Pharmacology, Department of Medicine..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tarek","family":"Absi","sequence":"additional","affiliation":[{"name":"From the Division of Cardiovascular Medicine, Davis Heart and Lung Research Institute (B.Z., D.G.W., Z.X., R.H., H.H., S.V., J.L.Z.), Department of Physiology and Cell Biology (B.Z., J.L.Z., M.J.K., M.T.Z.), The Ohio State University, Columbus; Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, HuBei, China (B.Z.); Department of Biostatistics (Y.S., M.X., F.E.H.), Division of Clinical Pharmacology, Department of Medicine..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark J.","family":"Kohr","sequence":"additional","affiliation":[{"name":"From the Division of Cardiovascular Medicine, Davis Heart and Lung Research Institute (B.Z., D.G.W., Z.X., R.H., H.H., S.V., J.L.Z.), Department of Physiology and Cell Biology (B.Z., J.L.Z., M.J.K., M.T.Z.), The Ohio State University, Columbus; Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, HuBei, China (B.Z.); Department of Biostatistics (Y.S., M.X., F.E.H.), Division of Clinical Pharmacology, Department of Medicine..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark T.","family":"Ziolo","sequence":"additional","affiliation":[{"name":"From the Division of Cardiovascular Medicine, Davis Heart and Lung Research Institute (B.Z., D.G.W., Z.X., R.H., H.H., S.V., J.L.Z.), Department of Physiology and Cell Biology (B.Z., J.L.Z., M.J.K., M.T.Z.), The Ohio State University, Columbus; Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, HuBei, China (B.Z.); Department of Biostatistics (Y.S., M.X., F.E.H.), Division of Clinical Pharmacology, Department of Medicine..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dan M.","family":"Roden","sequence":"additional","affiliation":[{"name":"From the Division of Cardiovascular Medicine, Davis Heart and Lung Research Institute (B.Z., D.G.W., Z.X., R.H., H.H., S.V., J.L.Z.), Department of Physiology and Cell Biology (B.Z., J.L.Z., M.J.K., M.T.Z.), The Ohio State University, Columbus; 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