{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,7]],"date-time":"2026-03-07T04:07:38Z","timestamp":1772856458242,"version":"3.50.1"},"reference-count":43,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Arrhythmia and Electrophysiology"],"published-print":{"date-parts":[[2015,12]]},"abstract":"<jats:sec>\n            <jats:title>Background\u2014<\/jats:title>\n            <jats:p>Hypercholesterolemia protects against ventricular fibrillation in patients with myocardial infarction. We hypothesize that hypercholesterolemia protects against ischemia-induced reentrant arrhythmias because of altered ion channel function.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods and Results\u2014<\/jats:title>\n            <jats:p>\n              ECGs were measured in low-density lipoprotein receptor knockout (LDLr\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              ), apolipoprotein A1 knockout (ApoA1\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              ), and wild-type (WT) mice. Action potentials, calcium handling, and ion currents were recorded in ventricular myocytes. Gene expression was determined by quantitative polymerase chain reaction and Western blot. In isolated perfused hearts, regional ischemia was induced and arrhythmia inducibility was tested. Serum low-density lipoprotein (LDL) cholesterol was higher in LDLr\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              mice than in WT mice (2.6 versus 0.4 mmol\/L), and high-density lipoprotein cholesterol was significantly lower in ApoA1\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              mice than in WT mice (0.3 versus 1.8 mmol\/L). LDLr\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              and ApoA1\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              myocytes contained more cholesterol than WT (34.4\u00b12.8 and 36.5\u00b12.4 versus 25.5\u00b10.4 \u03bcmol\/g protein). The major potassium currents were not different in LDLr\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              and ApoA1\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              compared with WT mice. The L-type calcium current (\n              <jats:italic>I<\/jats:italic>\n              <jats:sub>Ca<\/jats:sub>\n              ), however, was larger in LDLr\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              and ApoA1\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              than in WT (12.1\u00b10.7 and 12.8\u00b10.8 versus 9.4\u00b11.1 pA\/pF). Calcium transient amplitude and fractional sarcoplasmic reticulum calcium release were larger and action potential and QTc duration longer in LDLr\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              and ApoA1\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              than in WT mice (action potential duration at 90% of repolarization: 102\u00b14 and 106\u00b13 versus 84\u00b13.1 ms; QTc: 50.9\u00b11.3 and 52.8\u00b10.8 versus 43.5\u00b11.2 ms). During ischemia, ventricular tachycardia\/ventricular fibrillation inducibility was larger in WT than in LDLr\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              and ApoA1\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              hearts. Expression of sodium channel and Ca-handling genes were not significantly different between groups.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>\n              Dyscholesterolemia is associated with action potential prolongation because of increased\n              <jats:italic>I<\/jats:italic>\n              <jats:sub>Ca<\/jats:sub>\n              and reduces occurrence of reentrant arrhythmias during ischemia.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circep.115.002751","type":"journal-article","created":{"date-parts":[[2015,10,2]],"date-time":"2015-10-02T02:38:54Z","timestamp":1443753534000},"page":"1481-1490","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":26,"title":["Dyscholesterolemia Protects Against Ischemia-Induced Ventricular Arrhythmias"],"prefix":"10.1161","volume":"8","author":[{"given":"Antonius","family":"Baartscheer","sequence":"first","affiliation":[{"name":"Departments of Clinical and Experimental Cardiology (A.B., C.A.S., V.W., M.W.V., R.J.v.O., I.E., R.C.), Anatomy Embryology and Physiology (A.O.V.), and Medical Biochemistry (R.O., C.v.R., H.A.), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; and IHU Institut de Rythmologie et Mod\u00e9lisation Cardiaque, Fondation Bordeaux Universit\u00e9, Bordeaux, France (R.C.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cees A.","family":"Schumacher","sequence":"additional","affiliation":[{"name":"Departments of Clinical and Experimental Cardiology (A.B., C.A.S., V.W., M.W.V., R.J.v.O., I.E., R.C.), Anatomy Embryology and Physiology (A.O.V.), and Medical Biochemistry (R.O., C.v.R., H.A.), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; and IHU Institut de Rythmologie et Mod\u00e9lisation Cardiaque, Fondation Bordeaux Universit\u00e9, Bordeaux, France (R.C.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vincent","family":"Wekker","sequence":"additional","affiliation":[{"name":"Departments of Clinical and Experimental Cardiology (A.B., C.A.S., V.W., M.W.V., R.J.v.O., I.E., R.C.), Anatomy Embryology and Physiology (A.O.V.), and Medical Biochemistry (R.O., C.v.R., H.A.), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; and IHU Institut de Rythmologie et Mod\u00e9lisation Cardiaque, Fondation Bordeaux Universit\u00e9, Bordeaux, France (R.C.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arie O.","family":"Verkerk","sequence":"additional","affiliation":[{"name":"Departments of Clinical and Experimental Cardiology (A.B., C.A.S., V.W., M.W.V., R.J.v.O., I.E., R.C.), Anatomy Embryology and Physiology (A.O.V.), and Medical Biochemistry (R.O., C.v.R., H.A.), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; and IHU Institut de Rythmologie et Mod\u00e9lisation Cardiaque, Fondation Bordeaux Universit\u00e9, Bordeaux, France (R.C.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marieke W.","family":"Veldkamp","sequence":"additional","affiliation":[{"name":"Departments of Clinical and Experimental Cardiology (A.B., C.A.S., V.W., M.W.V., R.J.v.O., I.E., R.C.), Anatomy Embryology and Physiology (A.O.V.), and Medical Biochemistry (R.O., C.v.R., H.A.), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; and IHU Institut de Rythmologie et Mod\u00e9lisation Cardiaque, Fondation Bordeaux Universit\u00e9, Bordeaux, France (R.C.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ralph J.","family":"van Oort","sequence":"additional","affiliation":[{"name":"Departments of Clinical and Experimental Cardiology (A.B., C.A.S., V.W., M.W.V., R.J.v.O., I.E., R.C.), Anatomy Embryology and Physiology (A.O.V.), and Medical Biochemistry (R.O., C.v.R., H.A.), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; and IHU Institut de Rythmologie et Mod\u00e9lisation Cardiaque, Fondation Bordeaux Universit\u00e9, Bordeaux, France (R.C.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ies","family":"Elzenaar","sequence":"additional","affiliation":[{"name":"Departments of Clinical and Experimental Cardiology (A.B., C.A.S., V.W., M.W.V., R.J.v.O., I.E., R.C.), Anatomy Embryology and Physiology (A.O.V.), and Medical Biochemistry (R.O., C.v.R., H.A.), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; and IHU Institut de Rythmologie et Mod\u00e9lisation Cardiaque, Fondation Bordeaux Universit\u00e9, Bordeaux, France (R.C.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roelof","family":"Ottenhoff","sequence":"additional","affiliation":[{"name":"Departments of Clinical and Experimental Cardiology (A.B., C.A.S., V.W., M.W.V., R.J.v.O., I.E., R.C.), Anatomy Embryology and Physiology (A.O.V.), and Medical Biochemistry (R.O., C.v.R., H.A.), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; and IHU Institut de Rythmologie et Mod\u00e9lisation Cardiaque, Fondation Bordeaux Universit\u00e9, Bordeaux, France (R.C.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cindy","family":"van Roomen","sequence":"additional","affiliation":[{"name":"Departments of Clinical and Experimental Cardiology (A.B., C.A.S., V.W., M.W.V., R.J.v.O., I.E., R.C.), Anatomy Embryology and Physiology (A.O.V.), and Medical Biochemistry (R.O., C.v.R., H.A.), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; and IHU Institut de Rythmologie et Mod\u00e9lisation Cardiaque, Fondation Bordeaux Universit\u00e9, Bordeaux, France (R.C.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hans","family":"Aerts","sequence":"additional","affiliation":[{"name":"Departments of Clinical and Experimental Cardiology (A.B., C.A.S., V.W., M.W.V., R.J.v.O., I.E., R.C.), Anatomy Embryology and Physiology (A.O.V.), and Medical Biochemistry (R.O., C.v.R., H.A.), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; and IHU Institut de Rythmologie et Mod\u00e9lisation Cardiaque, Fondation Bordeaux Universit\u00e9, Bordeaux, France (R.C.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruben","family":"Coronel","sequence":"additional","affiliation":[{"name":"Departments of Clinical and Experimental Cardiology (A.B., C.A.S., V.W., M.W.V., R.J.v.O., I.E., R.C.), Anatomy Embryology and Physiology (A.O.V.), and Medical Biochemistry (R.O., C.v.R., H.A.), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; and IHU Institut de Rythmologie et Mod\u00e9lisation Cardiaque, Fondation Bordeaux Universit\u00e9, Bordeaux, France (R.C.)."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1388-1981(00)00156-6"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.105.606145"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-90-481-8622-8_19"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2005.11.013"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2006.02.022"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardfail.2005.06.439"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2010.11.072"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9149(99)80700-0"},{"key":"e_1_3_3_10_2","first-page":"105","article-title":"Afterdepolarizations and triggered activity.","volume":"87","author":"Fozzard HA.","year":"1992","unstructured":"Fozzard HA. 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