{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T08:42:51Z","timestamp":1790844171611,"version":"4.1.0"},"reference-count":70,"publisher":"Wiley","issue":"21","license":[{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["PG\/22\/11217"],"award-info":[{"award-number":["PG\/22\/11217"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["PG\/23\/11479"],"award-info":[{"award-number":["PG\/23\/11479"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:sec>\n                    <jats:title>Background and Purpose<\/jats:title>\n                    <jats:p>Autophagy is essential for cellular homeostasis, and its impairment contributes to cardiac hypertrophy. Modulating autophagy has shown potential in treating pathological hypertrophy. Prolylcarboxypeptidase (PRCP), a lysosomal enzyme that hydrolyzes angiotensin II to Ang1\u20107, has an unclear role in cardiac autophagy and hypertrophy. This study explores PRCP\u2019s function in regulating autophagy under hypertrophic stress and its potential as a therapeutic target.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>\n                      Transverse aortic constriction (TAC) was used to induce hypertrophy in mice. PRCP\u2010knockout (PRCP\n                      <jats:sup>KO<\/jats:sup>\n                      ) mice were generated using CRISPR\/Cas9, while PRCP was overexpressed in the heart using adeno\u2010associated virus 9. Cardiac function was evaluated via echocardiography and histological analysis. Autophagy markers were assessed by immunostaining, electron microscopy, and protein expression. In vitro, PRCP expression was manipulated in H9c2 cells. A novel DUBTAC compound was also synthesized to stabilize PRCP, and its protective effects were tested in H9c2 cells and hESC\u2010derived cardiomyocytes under isoprenaline\u2010induced stress.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>\n                      PRCP\n                      <jats:sup>KO<\/jats:sup>\n                      mice developed more severe cardiac hypertrophy, fibrosis, and diastolic dysfunction after TAC. These mice showed reduced autophagosome formation and decreased expression of autophagy\u2010related proteins WDR1 and WIPI1. In contrast, PRCP overexpression mitigated hypertrophy and preserved autophagy. Mechanistically, PRCP regulated autophagy via the interaction of WDR1 with WIPI1. Stabilizing PRCP with DUBTAC prevented its degradation and maintained autophagy under hypertrophic conditions.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and Implications<\/jats:title>\n                    <jats:p>PRCP is a previously unrecognized regulator of autophagy in the heart. Enhancing PRCP expression or stabilizing it pharmacologically via DUBTAC represents a novel and effective therapeutic approach for managing pathological cardiac hypertrophy and improving cardiac health.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.70094","type":"journal-article","created":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T03:25:32Z","timestamp":1751340332000},"page":"5317-5339","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Stabilisation of PRCP by deubiquitinase\u2010targeting chimera (DUBTAC) to replenish autophagy for ameliorating pathological cardiac hypertrophy"],"prefix":"10.1111","volume":"182","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8602-3427","authenticated-orcid":false,"given":"Fangchao","family":"Zhou","sequence":"first","affiliation":[{"name":"Division of Cardiovascular Science, Faculty of Biology, Medicine and Health The University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Xia","sequence":"additional","affiliation":[{"name":"Division of Pharmacy and Optometry, Faculty of Biology, Medicine and Health The University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingjuan","family":"Liu","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Science, Faculty of Biology, Medicine and Health The University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenqi","family":"He","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Science, Faculty of Biology, Medicine and Health The University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1012-4141","authenticated-orcid":false,"given":"Hongyuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Science, Faculty of Biology, Medicine and Health The University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernard D.","family":"Keavney","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Science, Faculty of Biology, Medicine and Health The University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Zi","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Science, Faculty of Biology, Medicine and Health The University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Binh Y.","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Science, Faculty of Biology, Medicine and Health The University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8435-808X","authenticated-orcid":false,"given":"Tamer M. 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