{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T14:54:26Z","timestamp":1769698466534,"version":"3.49.0"},"reference-count":56,"publisher":"American Diabetes Association","issue":"8","license":[{"start":{"date-parts":[[2024,5,21]],"date-time":"2024-05-21T00:00:00Z","timestamp":1716249600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.diabetesjournals.org\/journals\/pages\/license"}],"funder":[{"DOI":"10.13039\/501100000035","name":"Institute of Nutrition, Metabolism and Diabetes","doi-asserted-by":"publisher","award":["CIHR PJT-178134"],"award-info":[{"award-number":["CIHR PJT-178134"]}],"id":[{"id":"10.13039\/501100000035","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100013528","name":"Diabetes Canada","doi-asserted-by":"publisher","award":["OG-3-21-5585-BR"],"award-info":[{"award-number":["OG-3-21-5585-BR"]}],"id":[{"id":"10.13039\/100013528","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,8,1]]},"abstract":"<jats:sec>\n                  <jats:title\/>\n                  <jats:p>In addition to controlling smooth muscle tone in coronary vessels, endothelial cells also influence subjacent cardiomyocyte growth. Because heparanase, with exclusive expression in endothelial cells, enables extracellular matrix remodeling, angiogenesis, metabolic reprogramming, and cell survival, it is conceivable that it could also encourage development of cardiac hypertrophy. Global heparanase overexpression resulted in physiologic cardiac hypertrophy, likely an outcome of HSPG clustering and activation of hypertrophic signaling. The heparanase autocrine effect of releasing neuregulin-1 could have also contributed to this overexpression. Hyperglycemia induced by streptozotocin-induced diabetes sensitized the heart to flow-induced release of heparanase and neuregulin-1. Despite this excess secretion, progression of diabetes caused significant gene expression changes related to mitochondrial metabolism and cell death that led to development of pathologic hypertrophy and heart dysfunction. Physiologic cardiac hypertrophy was also observed in rats with cardiomyocyte-specific vascular endothelial growth factor B overexpression. When perfused, hearts from these animals released significantly higher amounts of both heparanase and neuregulin-1. However, subjecting these animals to diabetes triggered robust transcriptome changes related to metabolism and a transition to pathologic hypertrophy. Our data suggest that in the absence of mechanisms that support cardiac energy generation and prevention of cell death, as seen after diabetes, there is a transition from physiologic to pathologic cardiac hypertrophy and a decline in cardiac function.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Article Highlights<\/jats:title>\n               <\/jats:sec>","DOI":"10.2337\/db24-0217","type":"journal-article","created":{"date-parts":[[2024,5,21]],"date-time":"2024-05-21T18:35:05Z","timestamp":1716316505000},"page":"1300-1316","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":4,"title":["Heparanase Stimulation of Physiologic Cardiac Hypertrophy Is Suppressed After Chronic Diabetes, Resulting in Cardiac Remodeling and Dysfunction"],"prefix":"10.2337","volume":"73","author":[{"given":"Chae Syng","family":"Lee","sequence":"first","affiliation":[{"name":"1Faculty of 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