{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T19:49:41Z","timestamp":1787168981914,"version":"build-2736575974"},"reference-count":52,"publisher":"The Company of Biologists","license":[{"start":{"date-parts":[[2021,5,18]],"date-time":"2021-05-18T00:00:00Z","timestamp":1621296000000},"content-version":"am","delay-in-days":3059,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Summary<\/jats:title>\n                  <jats:p>In response to stress and extracellular signals, the heart undergoes a process called cardiac hypertrophy during which cardiomyocytes increase in size. If untreated, cardiac hypertrophy can progress to overt heart failure that causes significant morbidity and mortality. The identification of molecular signals that cause or modify cardiomyopathies is necessary to understand how the normal heart progresses to cardiac hypertrophy and heart failure. Receptor tyrosine kinase (RTK) signaling is essential for normal human cardiac function, and the inhibition of RTKs can cause dilated cardiomyopathies. However, neither investigations of activated RTK signaling pathways nor the characterization of hypertrophic cardiomyopathy in the adult fly heart has been previously described. Therefore, we developed strategies using Drosophila as a model to circumvent some of the complexities associated with mammalian models of cardiovascular disease. Transgenes encoding activated EGFRA887T, Ras85DV12 and Ras85DV12S35, which preferentially signal to Raf, or constitutively active human or fly Raf caused hypertrophic cardiomyopathy as determined by decreased end diastolic lumen dimensions, abnormal cardiomyocyte fiber morphology and increased heart wall thicknesses. There were no changes in cardiomyocyte cell numbers. Additionally, activated Raf also induced an increase in cardiomyocyte ploidy compared with control hearts. However, preventing increases in cardiomyocyte ploidy using fizzy-related (Fzr) RNAi did not rescue Raf-mediated cardiac hypertrophy, suggesting that Raf-mediated polyploidization is not required for cardiac hypertrophy. Similar to mammals, the cardiac-specific expression of RNAi directed against MEK or ERK rescued Raf-mediated cardiac hypertrophy. However, the cardiac-specific expression of activated ERKD334N, which promotes hyperplasia in non-cardiac tissues, did not cause myocyte hypertrophy. These results suggest that ERK is necessary, but not sufficient, for Raf-mediated cardiac hypertrophy.<\/jats:p>","DOI":"10.1242\/dmm.011361","type":"journal-article","created":{"date-parts":[[2013,4,5]],"date-time":"2013-04-05T00:18:19Z","timestamp":1365121099000},"source":"Crossref","is-referenced-by-count":25,"title":["Raf-mediated cardiac hypertrophy in adult\n                    <i>Drosophila<\/i>"],"prefix":"10.1242","author":[{"given":"Lin","family":"Yu","sequence":"first","affiliation":[{"name":"Duke University Medical Center, Durham, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Daniels","sequence":"additional","affiliation":[{"name":"Duke University Medical Center, Durham, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex E.","family":"Glaser","sequence":"additional","affiliation":[{"name":"Duke University Medical Center, Durham, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew J.","family":"Wolf","sequence":"additional","affiliation":[{"name":"Duke University Medical Center, Durham, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2013,1,1]]},"reference":[{"key":"2021042501091100100_b1-0060964","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/S0022-2828(86)80981-6","article-title":"Myocardial DNA content, ploidy level and cell number in geriatric hearts: post-mortem examinations of human myocardium in old age","volume":"18","author":"Adler","year":"1986","journal-title":"J. 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