{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T03:53:29Z","timestamp":1783569209889,"version":"3.55.0"},"reference-count":57,"publisher":"Portland Press Ltd.","issue":"3","license":[{"start":{"date-parts":[[2020,1,27]],"date-time":"2020-01-27T00:00:00Z","timestamp":1580083200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,2,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Hypertensive cardiac hypertrophy (HCH) is a common cause of heart failure (HF), a major public health problem worldwide. However, the molecular bases of HCH have not been completely elucidated. Neuron-derived orphan receptor-1 (NOR-1) is a nuclear receptor whose role in cardiac remodelling is poorly understood. The aim of the present study was to generate a transgenic mouse over-expressing NOR-1 in the heart (TgNOR-1) and assess the impact of this gain-of-function on HCH. The CAG promoter-driven transgenesis led to viable animals that over-expressed NOR-1 in the heart, mainly in cardiomyocytes and also in cardiofibroblasts. Cardiomyocytes from TgNOR-1 exhibited an enhanced cell surface area and myosin heavy chain 7 (Myh7)\/Myh6 expression ratio, and increased cell shortening elicited by electric field stimulation. TgNOR-1 cardiofibroblasts expressed higher levels of myofibroblast markers than wild-type (WT) cells (\u03b1 1 skeletal muscle actin (Acta1), transgelin (Sm22\u03b1)) and were more prone to synthesise collagen and migrate. TgNOR-1 mice experienced an age-associated remodelling of the left ventricle (LV). Angiotensin II (AngII) induced the cardiac expression of NOR-1, and NOR-1 transgenesis exacerbated AngII-induced cardiac hypertrophy and fibrosis. This effect was associated with the up-regulation of hypertrophic (brain natriuretic peptide (Bnp), Acta1 and Myh7) and fibrotic markers (collagen type I \u03b1 1 chain (Col1a1), Pai-1 and lysyl oxidase-like 2 (Loxl2)). NOR-1 transgenesis up-regulated two key genes involved in cardiac hypertrophy (Myh7, encoding for \u03b2-myosin heavy chain (\u03b2-MHC)) and fibrosis (Loxl2, encoding for the extracellular matrix (ECM) modifying enzyme, Loxl2). Interestigly, in transient transfection assays, NOR-1 drove the transcription of Myh7 and Loxl2 promoters. Our findings suggest that NOR-1 is involved in the transcriptional programme leading to HCH.<\/jats:p>","DOI":"10.1042\/cs20191014","type":"journal-article","created":{"date-parts":[[2020,1,27]],"date-time":"2020-01-27T11:20:01Z","timestamp":1580124001000},"page":"359-377","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Neuron-derived orphan receptor-1 modulates cardiac gene expression and exacerbates angiotensin II-induced cardiac hypertrophy"],"prefix":"10.1042","volume":"134","author":[{"given":"Laia","family":"Ca\u00f1es","sequence":"first","affiliation":[{"name":"Instituto de Investigaciones Biom\u00e9dicas de Barcelona (IIBB-CSIC), Barcelona, Spain"},{"name":"CIBER de Enfermedades Cardiovasculares, Instituto de Salud Carlos III, Madrid, Spain"},{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica Sant Pau (IIB-Sant Pau), Barcelona, 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de Veterinaria, Instituto de Investigaci\u00f3n Sanitaria de Arag\u00f3n-Universidad de Zaragoza, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leif","family":"Hove-Madsen","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Biom\u00e9dicas de Barcelona (IIBB-CSIC), Barcelona, Spain"},{"name":"CIBER de Enfermedades Cardiovasculares, Instituto de Salud Carlos III, Madrid, Spain"},{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica Sant Pau (IIB-Sant Pau), Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"CIBER de Enfermedades Cardiovasculares, Instituto de Salud Carlos III, Madrid, Spain"},{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica Sant Pau (IIB-Sant Pau), Barcelona, Spain"},{"name":"Institut de Recerca Hospital de la Santa Creu i Sant Pau-Programa ICCC, Barcelona, 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