دورية أكاديمية
Heparanase Stimulation of Physiologic Cardiac Hypertrophy Is Suppressed After Chronic Diabetes, Resulting in Cardiac Remodeling and Dysfunction.
| العنوان: | Heparanase Stimulation of Physiologic Cardiac Hypertrophy Is Suppressed After Chronic Diabetes, Resulting in Cardiac Remodeling and Dysfunction. |
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| المؤلفون: | Lee CS; Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia, Canada., Shang R; Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia, Canada., Wang F; School of Life Science and Technology, Key Laboratory of Developmental Genes and Human Disease, Southeast University, Nanjing, China., Khayambashi P; Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia, Canada., Wang H; Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia, Canada., Araujo G; Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia, Canada., Puri K; Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia, Canada., Vlodavsky I; Cancer and Vascular Biology Research Center, Rappaport Faculty of Medicine, Technion, Haifa, Israel., Hussein B; Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia, Canada., Rodrigues B; Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia, Canada. |
| المصدر: | Diabetes [Diabetes] 2024 Aug 01; Vol. 73 (8), pp. 1300-1316. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Diabetes Association Country of Publication: United States NLM ID: 0372763 Publication Model: Print Cited Medium: Internet ISSN: 1939-327X (Electronic) Linking ISSN: 00121797 NLM ISO Abbreviation: Diabetes Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Alexandria, VA : American Diabetes Association Original Publication: [New York, American Diabetes Association] |
| مواضيع طبية MeSH: | Cardiomegaly*/metabolism , Cardiomegaly*/pathology , Diabetes Mellitus, Experimental*/metabolism , Glucuronidase*/metabolism , Glucuronidase*/genetics , Ventricular Remodeling*/physiology, Animals ; Male ; Rats ; Myocytes, Cardiac/metabolism ; Myocytes, Cardiac/pathology ; Neuregulin-1/metabolism ; Neuregulin-1/genetics ; Female |
| مستخلص: | 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. (© 2024 by the American Diabetes Association.) |
| معلومات مُعتمدة: | CIHR PJT-178134 Institute of Nutrition, Metabolism and Diabetes; OG-3-21-5585-BR Diabetes Canada |
| المشرفين على المادة: | EC 3.2.1.31 (Glucuronidase) EC 3.2.1.- (heparanase) 0 (Neuregulin-1) |
| تواريخ الأحداث: | Date Created: 20240521 Date Completed: 20240719 Latest Revision: 20240724 |
| رمز التحديث: | 20240725 |
| DOI: | 10.2337/db24-0217 |
| PMID: | 38771953 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1939-327X |
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| DOI: | 10.2337/db24-0217 |