{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T13:13:27Z","timestamp":1783516407742,"version":"3.55.0"},"reference-count":32,"publisher":"Bioscientifica","issue":"2","content-domain":{"domain":["journals.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2007,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The natriuretic peptides, atrial (ANP) and brain natriuretic peptide (BNP) are known to suppress cardiac hypertrophy and fibrosis. Both ANP and BNP exert their bioactivities through the Npr1 receptor, and Npr1 knockout mice (Npr1\u2212\/\u2212) exhibit marked cardiac hypertrophy and fibrosis. In this study, we investigated which genes within the hypertrophic and fibrotic pathways are influenced by the lack of Npr1 signalling. cDNA microarray and quantitative real-time PCR (RT-PCR) analyses were performed on cardiac ventricles from Npr1\u2212\/\u2212mice. Gene expression at early and late stages during development of hypertrophy wasinvestigated in male and female Npr1\u2212\/\u2212mice at8 weeks and 6 months of age. Heart weight to body weight ratios (HW:BW) were maximally increased in 8-week males (P &amp;lt; 0.01), whilst HW:BW in females continued to increase progressively up to 6 months (P &amp;lt; 0.01). This was despite blood pressure being similarly elevated at both the ages in male and female knockout when compared with wild-type (WT) mice (P &amp;lt; 0.001). Microarray analysis identified altered gene expression at the earliest steps in the hypertrophy-signalling cascade in Npr1\u2212\/\u2212 mice, particularly calcium\u2013calmodulin signalling and ion channels, with subsequent changes in the expression of intracellular messengers including protein kinases and transcription factors. Real-time PCR analysis confirmed significant differences in gene expression of ANP, BNP, calmodulin 1, histone deacetylase 7a (HDAC7a), protein kinase C (PKC)\u03b9, (GATA) 4, collagen 1, phospholamban and transforming growth factor-\u03b21 in Npr1\u2212\/\u2212 mice when compared with WT (P &amp;lt; 0.05). The present study implicates the calmodulin\u2013CaMK\u2013Hdac\u2013Mef2 and PKC\u2013MAPK\u2013GATA4 pathways in Npr1 mediation of cardiac hypertrophy.<\/jats:p>","DOI":"10.1677\/jme.1.02138","type":"journal-article","created":{"date-parts":[[2007,2,9]],"date-time":"2007-02-09T11:33:01Z","timestamp":1171020781000},"page":"245-257","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-6","source":"Crossref","is-referenced-by-count":65,"title":["Npr1-regulated gene pathways contributing to cardiac hypertrophy and fibrosis"],"prefix":"10.1530","volume":"38","author":[{"given":"Leigh J","family":"Ellmers","sequence":"first","affiliation":[{"name":"Christchurch Cardioendocrine Research Group, Department of Medicine, Christchurch School of Medicine and Health Sciences, PO Box 4345, Christchurch, New Zealand 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola J A","family":"Scott","sequence":"additional","affiliation":[{"name":"Christchurch Cardioendocrine Research Group, Department of Medicine, Christchurch School of Medicine and Health Sciences, PO Box 4345, Christchurch, New Zealand 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jarkko","family":"Piuhola","sequence":"additional","affiliation":[{"name":"Christchurch Cardioendocrine Research Group, Department of Medicine, Christchurch School of Medicine and Health Sciences, PO Box 4345, Christchurch, New Zealand 1"},{"name":"Department of Pharmacology and Toxicology, Biocenter Oulu, University of Oulu, 90014 Oulu, Finland 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuyo","family":"Maeda","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, North Carolina 27599-7525, USA 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver","family":"Smithies","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, North Carolina 27599-7525, USA 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris M","family":"Frampton","sequence":"additional","affiliation":[{"name":"Christchurch Cardioendocrine Research Group, Department of Medicine, Christchurch School of Medicine and Health Sciences, PO Box 4345, Christchurch, New Zealand 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A Mark","family":"Richards","sequence":"additional","affiliation":[{"name":"Christchurch Cardioendocrine Research Group, Department of Medicine, Christchurch School of Medicine and Health Sciences, PO Box 4345, Christchurch, New Zealand 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vicky A","family":"Cameron","sequence":"additional","affiliation":[{"name":"Christchurch Cardioendocrine Research Group, Department of Medicine, Christchurch School of Medicine and Health Sciences, PO Box 4345, Christchurch, New Zealand 1"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"2026070808153701600_ADAZAWA-AND-KOMURO-2003","unstructured":"Adazawa\n              H\n            \n           & Komuro I 2003 Roles of cardiac transcription factors in cardiac hypertrophy. 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