{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T22:41:18Z","timestamp":1794004878261,"version":"4.8.0"},"reference-count":47,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2019,3,23]],"date-time":"2019-03-23T00:00:00Z","timestamp":1553299200000},"content-version":"vor","delay-in-days":2,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"British Heart Foundation Programme Grant","award":["RG\/16\/7\/32357"],"award-info":[{"award-number":["RG\/16\/7\/32357"]}]},{"name":"British Heart Foundation Programme Grant","award":["FS\/13\/58\/30648"],"award-info":[{"award-number":["FS\/13\/58\/30648"]}]},{"name":"NHLBI Institute of the US"},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HL089847"],"award-info":[{"award-number":["HL089847"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HL105993"],"award-info":[{"award-number":["HL105993"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Aims<\/jats:title>\n                  <jats:p>C-type natriuretic peptide (CNP) is an essential endothelium-derived signalling species that governs vascular homoeostasis; CNP is also expressed in the heart but an intrinsic role for the peptide in cardiac function is not established. Herein, we employ unique transgenic strains with cell-specific deletion of CNP to define a central (patho)physiological capacity of CNP in maintaining heart morphology and contractility.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and results<\/jats:title>\n                  <jats:p>Cardiac structure and function were explored in wild type (WT), cardiomyocyte (cmCNP\u2212\/\u2212), endothelium (ecCNP\u2212\/\u2212), and fibroblast (fbCNP\u2212\/\u2212)\u2014specific CNP knockout mice, and global natriuretic peptide receptor (NPR)-B\u2212\/\u2212, and NPR-C\u2212\/\u2212 animals at baseline and in experimental models of myocardial infarction and heart failure (HF). Endothelium-specific deletion of CNP resulted in impaired coronary responsiveness to endothelium-dependent- and flow-mediated-dilatation; changes mirrored in NPR-C\u2212\/\u2212 mice. Ex vivo, global ischaemia resulted in larger infarcts and diminished functional recovery in cmCNP\u2212\/\u2212 and NPR-C\u2212\/\u2212, but not ecCNP\u2212\/\u2212, vs. WT. The cardiac phenotype of cmCNP\u2212\/\u2212, fbCNP\u2212\/\u2212, and NPR-C\u2212\/\u2212 (but not ecCNP\u2212\/\u2212 or NPR-B\u2212\/\u2212) mice was more severe in pressure overload- and sympathetic hyperactivation-induced HF compared with WT; these adverse effects were rescued by pharmacological CNP administration in WT, but not NPR-C\u2212\/\u2212, mice. At a molecular level, CNP\/NPR-C signalling is impaired in human HF but attenuates activation of well-validated pro-hypertrophic and pro-fibrotic pathways.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>C-type natriuretic peptide of cardiomyocyte, endothelial and fibroblast origins co-ordinates and preserves cardiac structure, function, and coronary vasoreactivity via activation of NPR-C. Targeting NPR-C may prove an innovative approach to treating HF and ischaemic cardiovascular disorders.<\/jats:p>\n                  <jats:p\/>\n               <\/jats:sec>","DOI":"10.1093\/eurheartj\/ehz093","type":"journal-article","created":{"date-parts":[[2019,2,18]],"date-time":"2019-02-18T04:25:16Z","timestamp":1550463916000},"page":"1006-1020","source":"Crossref","is-referenced-by-count":84,"title":["C-type natriuretic peptide co-ordinates cardiac structure and function"],"prefix":"10.1093","volume":"41","author":[{"given":"Amie J","family":"Moyes","sequence":"first","affiliation":[{"name":"William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London , Charterhouse Square, London EC1M 6BQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandy M","family":"Chu","sequence":"additional","affiliation":[{"name":"William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London , Charterhouse Square, London EC1M 6BQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aisah A","family":"Aubdool","sequence":"additional","affiliation":[{"name":"William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London , Charterhouse Square, London EC1M 6BQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew S","family":"Dukinfield","sequence":"additional","affiliation":[{"name":"William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London , Charterhouse Square, London EC1M 6BQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth B","family":"Margulies","sequence":"additional","affiliation":[{"name":"Heart Failure and Transplant Program, Perelman School of Medicine, University of Pennsylvania , Translational Research Center, 3400 Civic Center Boulevard, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"Kenneth C","family":"Bedi","sequence":"additional","affiliation":[{"name":"Heart Failure and Transplant Program, Perelman School of Medicine, University of Pennsylvania , Translational Research Center, 3400 Civic Center Boulevard, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kairbaan","family":"Hodivala-Dilke","sequence":"additional","affiliation":[{"name":"Barts Cancer Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London , Charterhouse Square, London EC1M 6BQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reshma S","family":"Baliga","sequence":"additional","affiliation":[{"name":"William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London , Charterhouse Square, London EC1M 6BQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian J","family":"Hobbs","sequence":"additional","affiliation":[{"name":"William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London , Charterhouse Square, London EC1M 6BQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,3,21]]},"reference":[{"key":"2022102616082991300_ehz093-B1","doi-asserted-by":"crossref","first-page":"4039","DOI":"10.1172\/JCI74281","article-title":"Endothelial C-type natriuretic peptide maintains vascular homeostasis","volume":"124","author":"Moyes","year":"2014","journal-title":"J Clin Invest"},{"key":"2022102616082991300_ehz093-B2","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1161\/HYPERTENSIONAHA.116.08219","article-title":"Endothelium-derived C-type natriuretic peptide contributes to blood pressure regulation by maintaining endothelial 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