{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T03:47:03Z","timestamp":1776138423456,"version":"3.50.1"},"reference-count":48,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2023,12,28]],"date-time":"2023-12-28T00:00:00Z","timestamp":1703721600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82074190"],"award-info":[{"award-number":["82074190"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Natural Science Foundation of Fujian Province for Distinguished Young Scholars","award":["2022J06027"],"award-info":[{"award-number":["2022J06027"]}]},{"name":"Scientific Research Foundation"},{"DOI":"10.13039\/501100008021","name":"Fujian University of Traditional Chinese Medicine","doi-asserted-by":"publisher","award":["XQB202201"],"award-info":[{"award-number":["XQB202201"]}],"id":[{"id":"10.13039\/501100008021","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Scientific Research Foundation"},{"name":"Shanghai Key Medical Discipline for Critical Care Medicine"},{"name":"Top-level Clinical Discipline Project of Shanghai Pudong"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background and Aims<\/jats:title>\n                  <jats:p>Anti-hypertensive agents are one of the most frequently used drugs worldwide. However, no blood pressure\u2013lowering strategy is superior to placebo with respect to survival in diabetic hypertensive patients. Previous findings show that Wnt co-receptors LDL receptor\u2013related proteins 5 and 6 (LRP5\/6) can directly bind to several G protein\u2013coupled receptors (GPCRs). Because angiotensin II type 1 receptor (AT1R) is the most important GPCR in regulating hypertension, this study examines the possible mechanistic association between LRP5\/6 and their binding protein Dickkopf-1 (DKK1) and activation of the AT1R and further hypothesizes that the LRP5\/6-GPCR interaction may affect hypertension and potentiate cardiac impairment in the setting of diabetes.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>The roles of serum DKK1 and DKK1-LRP5\/6 signalling in diabetic injuries were investigated in human and diabetic mice.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Blood pressure up-regulation positively correlated with serum DKK1 elevations in humans. Notably, LRP5\/6 physically and functionally interacted with AT1R. The loss of membrane LRP5\/6 caused by injection of a recombinant DKK1 protein or conditional LRP5\/6 deletions resulted in AT1R activation and hypertension, as well as \u03b2-arrestin1 activation and cardiac impairment, possibly because of multiple GPCR alterations. Importantly, unlike commonly used anti-hypertensive agents, administration of the anti-DKK1 neutralizing antibody effectively prevented diabetic cardiac impairment in mice.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>These findings establish a novel DKK1-LRP5\/6-GPCR pathway in inducing diabetic injuries and may resolve the long-standing conundrum as to why elevated blood DKK1 has deleterious effects. Thus, monitoring and therapeutic elimination of blood DKK1 may be a promising strategy to attenuate diabetic injuries.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/eurheartj\/ehad842","type":"journal-article","created":{"date-parts":[[2023,12,28]],"date-time":"2023-12-28T10:56:21Z","timestamp":1703760981000},"page":"688-703","source":"Crossref","is-referenced-by-count":13,"title":["Inhibition of a novel Dickkopf-1-LDL receptor\u2013related proteins 5 and 6 axis prevents diabetic cardiomyopathy in mice"],"prefix":"10.1093","volume":"45","author":[{"given":"En","family":"Ma","sequence":"first","affiliation":[{"name":"Innovation and Transformation Center, Collaborative Innovation Center for Rehabilitation Technology, Fujian Key Laboratory of Integrative Medicine on Geriatrics, Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine , 1 Qiuyang Road, Minhou, Fuzhou 350122 , China"},{"name":"Clinical and Translational Research Center, Research Institute 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