Thrombospondin-2 is essential for myocardial matrix integrity: increased expression identifies failure-prone cardiac hypertrophy
| Autor: | Chris T. Evelo, Yigal M. Pinto, Rudy F. J. J. Duisters, Harry J.G.M. Crijns, Jos F.M. Smits, Umesh C. Sharma, Jacques Debets, Blanche Schroen, Mat J.A.P. Daemen, Saraswati Pokharel, Jack P.M. Cleutjens, Rick van Leeuwen, Stephane Heymans, Ben J. A. Janssen, Paul Bornstein, J. Gordon Porter, W. Matthijs Blankesteijn |
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| Přispěvatelé: | Other departments, Cardiology, Computational Biology |
| Jazyk: | angličtina |
| Rok vydání: | 2004 |
| Předmět: |
medicine.medical_specialty
Heart disease Physiology Cardiac Output Low Heart Rupture Gene Expression Muscle hypertrophy Animals Genetically Modified Rats Sprague-Dawley Mice Internal medicine Renin Biopsy medicine Animals Humans Genetic Predisposition to Disease Collagenases Mice Knockout Enzyme Precursors Ejection fraction medicine.diagnostic_test business.industry Angiotensin II Gene Expression Profiling Myocardium Metalloendopeptidases Stroke Volume Stroke volume medicine.disease Extracellular Matrix Rats Up-Regulation Endocrinology Matrix Metalloproteinase 9 Gelatinases Heart failure Hypertension Circulatory system Disease Progression Cardiology Hypertrophy Left Ventricular Cardiomyopathies Thrombospondins Cardiology and Cardiovascular Medicine business |
| Zdroj: | Circulation research, 95(5), 515-522. Lippincott Williams and Wilkins Circulation Research, 95(5), 506-514. Lippincott Williams and Wilkins Ltd. |
| ISSN: | 0009-7330 |
| Popis: | Cardiac hypertrophy can lead to heart failure (HF), but it is unpredictable which hypertrophied myocardium will progress to HF. We surmised that apart from hypertrophy-related genes, failure-related genes are expressed before the onset of failure, permitting molecular prediction of HF. Hearts from hypertensive homozygous renin-overexpressing (Ren-2) rats that had progressed to early HF were compared by microarray analysis to Ren-2 rats that had remained compensated. To identify which HF-related genes preceded failure, cardiac biopsy specimens were taken during compensated hypertrophy and we then monitored whether the rat progressed to HF or remained compensated. Among 48 genes overexpressed in failing hearts, we focused on thrombospondin-2 (TSP2). TSP2 was selectively overexpressed only in biopsy specimens from rats that later progressed to HF. Moreover, expression of TSP2 was increased in human hypertrophied hearts with decreased (0.19±0.01) versus normal ejection fraction (0.11±0.03 [arbitrary units]; P P |
| Databáze: | OpenAIRE |
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