{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T19:17:20Z","timestamp":1793128640003,"version":"4.5.0"},"reference-count":47,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2013,3,12]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      Autophagy is critical in the maintenance of cellular protein quality control, the final step of which involves the fusion of autophagosomes with lysosomes. Cathepsin\u2010L (\n                      <jats:styled-content style=\"fixed-case\">CTSL<\/jats:styled-content>\n                      ) is a key member of the lysosomal protease family that is expressed in the murine and human heart, and it may play an important role in protein turnover. We hypothesized that\n                      <jats:styled-content style=\"fixed-case\">CTSL<\/jats:styled-content>\n                      is important in regulating protein processing in the heart, particularly under pathological stress.\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                      Phenylephrine\u2010induced cardiac hypertrophy in vitro was more pronounced in\n                      <jats:styled-content style=\"fixed-case\">CTSL<\/jats:styled-content>\n                      \u2010deficient neonatal cardiomyocytes than in in controls. This was accompanied by a significant accumulation of autophagosomes, increased levels of ubiquitin\u2010conjugated protein, as well as impaired protein degradation and decreased cell viability. These effects were partially rescued with\n                      <jats:italic>\n                        <jats:styled-content style=\"fixed-case\">CTSL<\/jats:styled-content>\n                        1\n                      <\/jats:italic>\n                      replacement via adeno\u2010associated virus\u2013mediated gene transfer. In the in vivo murine model of aortic banding (\n                      <jats:styled-content style=\"fixed-case\">AB<\/jats:styled-content>\n                      ), a deficiency in\n                      <jats:styled-content style=\"fixed-case\">CTSL<\/jats:styled-content>\n                      markedly exacerbated cardiac hypertrophy, worsened cardiac function, and increased mortality.\n                      <jats:italic>Ctsl<\/jats:italic>\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      <jats:styled-content style=\"fixed-case\">AB<\/jats:styled-content>\n                      mice demonstrated significantly decreased lysosomal activity and increased sarcomere\u2010associated protein aggregation. Homeostasis of the endoplasmic reticulum was also altered by\n                      <jats:styled-content style=\"fixed-case\">CTSL<\/jats:styled-content>\n                      deficiency, with increases in Bip and\n                      <jats:styled-content style=\"fixed-case\">GRP<\/jats:styled-content>\n                      94 proteins, accompanied by increased ubiquitin\u2013proteasome system activity and higher levels of ubiquitinated proteins in response to\n                      <jats:styled-content style=\"fixed-case\">AB<\/jats:styled-content>\n                      . These changes ultimately led to a decrease in cellular\n                      <jats:styled-content style=\"fixed-case\">ATP<\/jats:styled-content>\n                      production, enhanced oxidative stress, and increased cellular apoptosis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">Lysosomal CTSL attenuates cardiac hypertrophy and preserves cardiac function through facilitation of autophagy and proteasomal protein processing.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.113.000191","type":"journal-article","created":{"date-parts":[[2013,5,24]],"date-time":"2013-05-24T12:49:31Z","timestamp":1369399771000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":81,"title":["Cathepsin\u2010L Ameliorates Cardiac Hypertrophy Through Activation of the Autophagy\u2013Lysosomal Dependent Protein Processing Pathways"],"prefix":"10.1161","volume":"2","author":[{"given":"Mei","family":"Sun","sequence":"first","affiliation":[{"name":"Division of Cardiology, Heart and Stroke\/Richard Lewar Centre of Excellence, University Health Network, Toronto General Hospital, 200 Elizabeth Street, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maral","family":"Ouzounian","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Heart and Stroke\/Richard Lewar Centre of Excellence, University Health Network, Toronto General Hospital, 200 Elizabeth Street, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geoffrey","family":"de Couto","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Heart and Stroke\/Richard Lewar Centre of Excellence, University Health Network, Toronto General Hospital, 200 Elizabeth Street, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manyin","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Heart and Stroke\/Richard Lewar Centre of Excellence, University Health Network, Toronto General Hospital, 200 Elizabeth Street, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ran","family":"Yan","sequence":"additional","affiliation":[{"name":"McMaster University Medical School, Hamilton, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiro","family":"Fukuoka","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Heart and Stroke\/Richard Lewar Centre of Excellence, University Health Network, Toronto General Hospital, 200 Elizabeth Street, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guohua","family":"Li","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Heart and Stroke\/Richard Lewar Centre of Excellence, University Health Network, Toronto General Hospital, 200 Elizabeth Street, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Moon","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Heart and Stroke\/Richard Lewar Centre of Excellence, University Health Network, Toronto General Hospital, 200 Elizabeth Street, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youan","family":"Liu","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Heart and Stroke\/Richard Lewar Centre of Excellence, University Health Network, Toronto General Hospital, 200 Elizabeth Street, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Gramolini","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of Toronto and University Health 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