{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T05:32:29Z","timestamp":1789968749430,"version":"4.0.1"},"reference-count":52,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"7","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Heart Failure"],"published-print":{"date-parts":[[2017,7]]},"abstract":"<jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>Lysosomal dysfunction is implicated in human heart failure for which ischemic heart disease is the leading cause. Altered myocardial expression of CTSD (cathepsin D), a major lysosomal protease, was observed in human heart failure, but its pathophysiological significance has not been determined.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p>\n              Western blot analyses revealed an increase in the precursor but not the mature form of CTSD in myocardial samples from explanted human failing hearts with ischemic heart disease, which is recapitulated in chronic myocardial infarction produced via coronary artery ligation in\n              <jats:italic>Ctsd<\/jats:italic>\n              <jats:sup>+\/+<\/jats:sup>\n              but not\n              <jats:italic>Ctsd<\/jats:italic>\n              <jats:sup>\n                <jats:italic>+\/\u2212<\/jats:italic>\n              <\/jats:sup>\n              mice. Mice deficient of\n              <jats:italic>Ctsd<\/jats:italic>\n              displayed impaired myocardial autophagosome removal, reduced autophagic flux, and restrictive cardiomyopathy. After induction of myocardial infarction, weekly serial echocardiography detected earlier occurrence of left ventricle chamber dilatation, greater decreases in ejection fraction and fractional shortening, and lesser wall thickening throughout the first 4 weeks; pressure\u2013volume relationship analyses at 4 weeks revealed greater decreases in systolic and diastolic functions, stroke work, stroke volume, and cardiac output; greater increases in the ventricular weight to body weight and the lung weight to body weight ratios and larger scar size were also detected in\n              <jats:italic>Ctsd<\/jats:italic>\n              <jats:sup>\n                <jats:italic>+\/\u2212<\/jats:italic>\n              <\/jats:sup>\n              mice compared with\n              <jats:italic>Ctsd<\/jats:italic>\n              <jats:sup>\n                <jats:italic>+\/+<\/jats:italic>\n              <\/jats:sup>\n              mice. Significant increases of myocardial autophagic flux detected at 1 and 4 weeks after induction of myocardial infarction in the\n              <jats:italic>Ctsd<\/jats:italic>\n              <jats:sup>\n                <jats:italic>+\/+<\/jats:italic>\n              <\/jats:sup>\n              mice were diminished in the\n              <jats:italic>Ctsd<\/jats:italic>\n              <jats:sup>\n                <jats:italic>+\/\u2212<\/jats:italic>\n              <\/jats:sup>\n              mice.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>Myocardial CTSD upregulation induced by myocardial infarction protects against cardiac remodeling and malfunction, which is at least in part through promoting myocardial autophagic flux.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circheartfailure.117.004044","type":"journal-article","created":{"date-parts":[[2017,7,11]],"date-time":"2017-07-11T15:32:45Z","timestamp":1499787165000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":57,"title":["Myocardial Upregulation of Cathepsin D by Ischemic Heart Disease Promotes Autophagic Flux and Protects Against Cardiac Remodeling and Heart Failure"],"prefix":"10.1161","volume":"10","author":[{"given":"Penglong","family":"Wu","sequence":"first","affiliation":[{"name":"From the Department of Cardiology, Shanghai Jiao Tong University Affiliated Sixth People\u2019s Hospital, China (P.W., M.W., J.L., X.W.); Division of Basic Biomedical Sciences, Sanford School of Medicine of the University of South Dakota, Vermillion (P.W., X.W.); Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis (X.Y., F.L.); Department of Pathology, University of Alabama at Birmingham (J.Z.); Clinical Research Center and Division of Cardiology, Zhejiang University..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xun","family":"Yuan","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology, Shanghai Jiao Tong University Affiliated Sixth People\u2019s Hospital, China (P.W., M.W., J.L., X.W.); Division of Basic Biomedical Sciences, Sanford School of Medicine of the University of South Dakota, Vermillion (P.W., X.W.); Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis (X.Y., F.L.); Department of Pathology, University of Alabama at Birmingham (J.Z.); Clinical Research Center and Division of Cardiology, Zhejiang University..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faqian","family":"Li","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology, Shanghai Jiao Tong University Affiliated Sixth People\u2019s Hospital, China (P.W., M.W., J.L., X.W.); Division of Basic Biomedical Sciences, Sanford School of Medicine of the University of South Dakota, Vermillion (P.W., X.W.); Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis (X.Y., F.L.); Department of Pathology, University of Alabama at Birmingham (J.Z.); Clinical Research Center and Division of Cardiology, Zhejiang University..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianhua","family":"Zhang","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology, Shanghai Jiao Tong University Affiliated Sixth People\u2019s Hospital, China (P.W., M.W., J.L., X.W.); Division of Basic Biomedical Sciences, Sanford School of Medicine of the University of South Dakota, Vermillion (P.W., X.W.); Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis (X.Y., F.L.); Department of Pathology, University of Alabama at Birmingham (J.Z.); Clinical Research Center and Division of Cardiology, Zhejiang University..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zhu","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology, Shanghai Jiao Tong University Affiliated Sixth People\u2019s Hospital, China (P.W., M.W., J.L., X.W.); Division of Basic Biomedical Sciences, Sanford School of Medicine of the University of South Dakota, Vermillion (P.W., X.W.); Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis (X.Y., F.L.); Department of Pathology, University of Alabama at Birmingham (J.Z.); Clinical Research Center and Division of Cardiology, Zhejiang University..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Wei","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology, Shanghai Jiao Tong University Affiliated Sixth People\u2019s Hospital, China (P.W., M.W., J.L., X.W.); Division of Basic Biomedical Sciences, Sanford School of Medicine of the University of South Dakota, Vermillion (P.W., X.W.); Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis (X.Y., F.L.); Department of Pathology, University of Alabama at Birmingham (J.Z.); Clinical Research Center and Division of Cardiology, Zhejiang University..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingbo","family":"Li","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology, Shanghai Jiao Tong University Affiliated Sixth People\u2019s Hospital, China (P.W., M.W., J.L., X.W.); Division of Basic Biomedical Sciences, Sanford School of Medicine of the University of South Dakota, Vermillion (P.W., X.W.); Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis (X.Y., F.L.); Department of Pathology, University of Alabama at Birmingham (J.Z.); Clinical Research Center and Division of Cardiology, Zhejiang 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