{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T17:11:21Z","timestamp":1787937081704,"version":"build-2784847793"},"reference-count":57,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"7","license":[{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>Thoracic (TAA) and abdominal (AAA) aortic aneurysm are life-threatening diseases characterized by dilation, inflammation, and structural weakness; development of pharmacological therapies is desperately needed. CNP (C-type natriuretic peptide) plays a key role in vascular homeostasis, mediating vasodilator, anti-inflammatory, and antiatherogenic actions. Since such processes drive AA, we determined the role of endogenous CNP in offsetting pathogenesis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>\n                      Tissue from patients with AA was analyzed to determine the consequences on CNP signaling. Ascending and suprarenal aortic diameters were assessed at baseline and following Ang II (angiotensin II; 1.44 mg\/kg per day) infusion in wild-type, endothelium-restricted (ecCNP\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      ), fibroblast-restricted (fbCNP\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      ), global CNP (gbCNP\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      ), or global NPR-C\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice infected with an adeno-associated virus expressing a proprotein convertase subtilisin\/kexin type 9 gain-of-function mutation or backcrossed to an apoE\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      background. At 28 days, aortas were harvested for RT-qPCR (quantitative reverse transcription polymerase chain reaction) and histological analyses. CNP (0.2 mg\/kg per day) was infused to rescue any adverse phenotype.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>\n                      Aneurysmal tissue from patients with TAA and AAA revealed that CNP and NPR-C (natriuretic peptide receptor-C) expression were overtly perturbed. ecCNP\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      , fbCNP\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      , and gbCNP\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice exhibited an aggravated phenotype compared to wild-type animals in both ascending and suprarenal aortas, exemplified by greater dilation, fibrosis, elastin degradation, and macrophage infiltration. CNP and NPR-C expression was also dysregulated in murine thoracic AA and abdominal AA, accompanied by increased accumulation of mRNA encoding markers of inflammation, extracellular matrix remodeling\/calcification, fibrosis, and apoptosis. CNP also prevented activation of isolated macrophages and vascular smooth muscle cells. An essentially identical phenotype was observed in NPR-C\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice and while administration of CNP protected against disease severity in wild-type animals, this phenotypic rescue was not apparent in NPR-C\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>Endothelium- and fibroblast-derived CNP, via NPR-C activation, plays important roles in attenuating AA formation by preserving aortic structure and function. Therapeutic strategies aimed at mimicking CNP bioactivity hold potential to reduce the need for surgical intervention.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/atvbaha.124.322350","type":"journal-article","created":{"date-parts":[[2025,4,3]],"date-time":"2025-04-03T06:47:54Z","timestamp":1743662874000},"page":"1044-1063","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":9,"title":["Endothelium- and Fibroblast-Derived C-Type Natriuretic Peptide Prevents the Development and Progression of Aortic Aneurysm"],"prefix":"10.1161","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4712-9421","authenticated-orcid":true,"given":"Aisah A.","family":"Aubdool","sequence":"first","affiliation":[{"name":"William Harvey Research Institute, Faculty of Medicine and Dentistry, Barts &amp; The London Hospitals, Queen Mary University of London, United Kingdom (A.A.A., A.J.M., C.P.-T., R.S.B., J.S.S., M.T.S., K.J., A.K.P., A.J.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9336-9904","authenticated-orcid":true,"given":"Amie J.","family":"Moyes","sequence":"additional","affiliation":[{"name":"William Harvey Research Institute, Faculty of Medicine and Dentistry, Barts &amp; The London Hospitals, Queen Mary University of London, United Kingdom (A.A.A., A.J.M., C.P.-T., R.S.B., J.S.S., M.T.S., K.J., A.K.P., A.J.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2349-0642","authenticated-orcid":true,"given":"Cristina","family":"Perez-Ternero","sequence":"additional","affiliation":[{"name":"William Harvey Research Institute, Faculty of Medicine and Dentistry, Barts &amp; The London Hospitals, Queen Mary University of London, United Kingdom (A.A.A., A.J.M., C.P.-T., R.S.B., J.S.S., M.T.S., K.J., A.K.P., A.J.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5582-5152","authenticated-orcid":true,"given":"Reshma S.","family":"Baliga","sequence":"additional","affiliation":[{"name":"William Harvey Research Institute, Faculty of Medicine and Dentistry, Barts &amp; The London Hospitals, Queen Mary University of London, United Kingdom (A.A.A., A.J.M., C.P.-T., R.S.B., J.S.S., M.T.S., K.J., A.K.P., A.J.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaspinder Singh","family":"Sanghera","sequence":"additional","affiliation":[{"name":"William Harvey Research Institute, Faculty of Medicine and Dentistry, Barts &amp; The London Hospitals, Queen Mary University of London, United Kingdom (A.A.A., A.J.M., C.P.-T., R.S.B., J.S.S., M.T.S., K.J., A.K.P., A.J.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-3623-2075","authenticated-orcid":true,"given":"M. Taaha","family":"Syed","sequence":"additional","affiliation":[{"name":"William Harvey Research Institute, Faculty of Medicine and Dentistry, Barts &amp; The London Hospitals, Queen Mary University of London, United Kingdom (A.A.A., A.J.M., C.P.-T., R.S.B., J.S.S., M.T.S., K.J., A.K.P., A.J.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kareemah","family":"Jaigirdar","sequence":"additional","affiliation":[{"name":"William Harvey Research Institute, Faculty of Medicine and Dentistry, Barts &amp; The London Hospitals, Queen Mary University of London, United Kingdom (A.A.A., A.J.M., C.P.-T., R.S.B., J.S.S., M.T.S., K.J., A.K.P., A.J.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anmolpreet K.","family":"Panesar","sequence":"additional","affiliation":[{"name":"William Harvey Research Institute, Faculty of Medicine and Dentistry, Barts &amp; The London Hospitals, Queen Mary University of London, United Kingdom (A.A.A., A.J.M., C.P.-T., R.S.B., J.S.S., M.T.S., K.J., A.K.P., A.J.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6826-4211","authenticated-orcid":true,"given":"Janice C.","family":"Tsui","sequence":"additional","affiliation":[{"name":"Division of Surgery and Interventional Science, University College London and Royal Free London NHS Foundation Trust, United Kingdom (J.C.T.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8213-9166","authenticated-orcid":true,"given":"Yanming","family":"Li","sequence":"additional","affiliation":[{"name":"Division of Cardiothoracic Surgery, Michael E. 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