{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T14:58:33Z","timestamp":1784818713218,"version":"3.55.0"},"reference-count":77,"publisher":"American Physiological Society","issue":"1","funder":[{"DOI":"10.13039\/501100000222","name":"Heart and Stroke Foundation of Canada (Fondation des maladies du c\u0153ur du Canada)","doi-asserted-by":"publisher","award":["G-16-00014536"],"award-info":[{"award-number":["G-16-00014536"]}],"id":[{"id":"10.13039\/501100000222","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2018,1,1]]},"abstract":"<jats:p>In the diabetic heart, there is excessive dependence on fatty acid (FA) utilization to generate ATP. Lipoprotein lipase (LPL)-mediated hydrolysis of circulating triglycerides is suggested to be the predominant source of FA for cardiac utilization during diabetes. In the heart, the majority of LPL is synthesized in cardiomyocytes and secreted onto cell surface heparan sulfate proteoglycan (HSPG), where an endothelial cell (EC)-releasable \u03b2-endoglycosidase, heparanase cleaves the side chains of HSPG to liberate LPL for its onward movement across the EC. EC glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1) captures this released enzyme at its basolateral side and shuttles it across to its luminal side. We tested whether the diabetes-induced increase of transforming growth factor-\u03b2 (TGF-\u03b2) can influence the myocyte and EC to help transfer LPL to the vascular lumen to generate triglyceride-FA. In response to high glucose and EC heparanase secretion, this endoglycosidase is taken up by the cardiomyocyte (Wang Y, Chiu AP, Neumaier K, Wang F, Zhang D, Hussein B, Lal N, Wan A, Liu G, Vlodavsky I, Rodrigues B. Diabetes 63: 2643\u20132655, 2014) to stimulate matrix metalloproteinase-9 expression and the conversion of latent to active TGF-\u03b2. In the cardiomyocyte, TGF-\u03b2 activation of RhoA enhances actin cytoskeleton rearrangement to promote LPL trafficking and secretion onto cell surface HSPG. In the EC, TGF-\u03b2 signaling promotes mesodermal homeobox 2 translocation to the nucleus, which increases the expression of GPIHBP1, which facilitates movement of LPL to the vascular lumen. Collectively, our data suggest that in the diabetic heart, TGF-\u03b2 actions on the cardiomyocyte promotes movement of LPL, whereas its action on the EC facilitates LPL shuttling.<\/jats:p><jats:p>NEW &amp; NOTEWORTHY Endothelial cells, as first responders to hyperglycemia, release heparanase, whose subsequent uptake by cardiomyocytes amplifies matrix metalloproteinase-9 expression and activation of transforming growth factor-\u03b2. Transforming growth factor-\u03b2 increases lipoprotein lipase secretion from cardiomyocytes and promotes mesodermal homeobox 2 to enhance glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1-dependent transfer of lipoprotein lipase across endothelial cells, mechanisms that accelerate fatty acid utilization by the diabetic heart.<\/jats:p>","DOI":"10.1152\/ajpheart.00372.2017","type":"journal-article","created":{"date-parts":[[2017,10,7]],"date-time":"2017-10-07T01:15:17Z","timestamp":1507338917000},"page":"H82-H94","source":"Crossref","is-referenced-by-count":16,"title":["Dual effects of hyperglycemia on endothelial cells and cardiomyocytes to enhance coronary LPL activity"],"prefix":"10.1152","volume":"314","author":[{"given":"Amy Pei-Ling","family":"Chiu","sequence":"first","affiliation":[{"name":"Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, British Columbia, 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