Increased expression of adenosine triphosphate-sensitive K+ channels in mitral dysfunction: mechanically stimulated transcription and hypoxia-induced protein stability?
| Autor: | Raeis Dauvé, V., Philip Couderc, P., Faggian, Giuseppe, Tessari, Maddalena, Roatti, A., Milano, Aldo Domenico, Bochaton Piallat, M., Baertschi, A. J. |
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| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Male
Potassium Channels Myocardium/metabolism Messenger Blood Pressure Messenger/metabolism ddc:616.07 Mice Anoxia KATP Channels Anoxia/metabolism Hypoxia Kir6.2 expression Alpha Subunit/metabolism Mice Knockout Mitral Valve Insufficiency/metabolism Protein Stability Mitral Valve Insufficiency Heart Ventricles/metabolism Middle Aged Inwardly Rectifying KATP Channels/metabolism Aged Animals Anoxia metabolism Blood Gas Analysis Blood Pressure Echocardiography Female Gene Expression Regulation Heart Ventricles metabolism Humans Hypoxia-Inducible Factor 1 alpha Subunit metabolism KATP Channels metabolism Male Mice Mice Knockout Middle Aged Mitral Valve Insufficiency metabolism Myocardium metabolism Oxygen physiology Partial Pressure Potassium Channels metabolism Protein Stability RNA metabolism Stress Mechanical Echocardiography cardiovascular system Female Hypoxia-Inducible Factor 1 transcription endocrine system Heart Ventricles Knockout Partial Pressure Oxygen/physiology ischemia Stress Inwardly Rectifying/metabolism Animals Humans RNA Messenger Potassium Channels Inwardly Rectifying Aged Myocardium mechanical stress Hypoxia-Inducible Factor 1 alpha Subunit ddc:616.8 Oxygen Gene Expression Regulation physiology RNA Stress Mechanical mitral regurgitation ddc:618.92 Blood Gas Analysis metabolism |
| Zdroj: | Journal of the American College of Cardiology, Vol. 59, No 4 (2012) pp. 390-6 Journal of the American College of Cardiology |
| ISSN: | 0735-1097 |
| Popis: | OBJECTIVES The aim of this study was to test whether adenosine triphosphate sensitive K(+) (KATP) channel expression relates to mechanical and hypoxic stress within the left human heart. BACKGROUND The KATP channels play a vital role in preserving the metabolic integrity of the stressed heart. However the mechanisms that govern the expression of their subunits (e.g. potassium inward rectifier [Kir] 6.2) in adult pathologies are mostly unknown. METHODS We collected biopsies from the 4 cardiac chambers and 50 clinical parameters from 30 surgical patients with severe mitral dysfunction. Proteins and messenger ribonucleic acids (mRNAs) of KATP pore subunits and mRNAs of their known transcriptional regulators (forkhead box [FOX] F2 FOXO1 FOXO3 and hypoxia inducible factor [HIF] 1a) were measured respectively by Western blotting immunohistochemistry and quantitative real time polymerase chain reaction and submitted to statistical analysis. RESULTS In all heart chambers Kir6.2 mRNA correlated with HIF 1a mRNA. Neither Kir6.1 nor Kir6.2 proteins positively correlated with their respective mRNAs. The HIF 1a mRNA related in the left ventricle to aortic pressure in the left atrium to left atrial pressure and in all heart chambers to a decreased Kir6.2 protein/mRNA ratio. Interestingly in the left heart Kir6.2 protein and its immunohistochemical detection in myocytes were maximal at low venous PO(2). In the left ventricle the Kir6.2 protein/mRNA ratio was also significantly higher at low venous PO(2) suggesting that tissue hypoxia might stabilize the Kir6.2 protein. CONCLUSIONS Results suggest that post transcriptional events determine Kir6.2 protein expression in the left ventricle of patients with severe mitral dysfunction and low venous PO(2). Mechanical stress mainly affects transcription of HIF 1a and Kir6.2. This study implies that new therapies could aim at the proteasome for stabilizing the left ventricular Kir6.2 protein. |
| Databáze: | OpenAIRE |
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