دورية أكاديمية
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Synergistic effect on cardiac energetics by targeting the creatine kinase system: in vivo application of high-resolution 31 P-CMRS in the mouse.

التفاصيل البيبلوغرافية
العنوان: Synergistic effect on cardiac energetics by targeting the creatine kinase system: in vivo application of high-resolution 31 P-CMRS in the mouse.
المؤلفون: Maguire ML; Centre for Preclinical Imaging, University of Liverpool, Liverpool, UK., McAndrew DJ; Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK., Lake HA; Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK., Ostrowski PJ; Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK., Zervou S; Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK., Neubauer S; Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.; British Heart Foundation Centre for Research Excellence, University of Oxford, Oxford, UK., Lygate CA; Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK. craig.lygate@cardiov.ox.ac.uk.; British Heart Foundation Centre for Research Excellence, University of Oxford, Oxford, UK. craig.lygate@cardiov.ox.ac.uk., Schneider JE; Experimental and Preclinical Imaging Centre (ePIC), Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK. J.E.Schneider@leeds.ac.uk.
المصدر: Journal of cardiovascular magnetic resonance : official journal of the Society for Cardiovascular Magnetic Resonance [J Cardiovasc Magn Reson] 2023 Feb 06; Vol. 25 (1), pp. 6. Date of Electronic Publication: 2023 Feb 06.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Elsevier Country of Publication: England NLM ID: 9815616 Publication Model: Electronic Cited Medium: Internet ISSN: 1532-429X (Electronic) Linking ISSN: 10976647 NLM ISO Abbreviation: J Cardiovasc Magn Reson Subsets: MEDLINE
أسماء مطبوعة: Publication: 2024- : London : Elsevier
Original Publication: New York : M. Dekker, Inc., c1998-
مواضيع طبية MeSH: Creatine Kinase*/metabolism , Creatine*/metabolism, Mice ; Animals ; Energy Metabolism/physiology ; Predictive Value of Tests ; Myocardium/pathology ; Phosphocreatine/metabolism ; Adenosine Triphosphate/metabolism ; Mice, Transgenic
مستخلص: Background: Phosphorus cardiovascular magnetic resonance spectroscopy ( 31 P-CMRS) has emerged as an important tool for the preclinical assessment of myocardial energetics in vivo. However, the high rate and diminutive size of the mouse heart is a challenge, resulting in low resolution and poor signal-to-noise. Here we describe a refined high-resolution 31 P-CMRS technique and apply it to a novel double transgenic mouse (dTg) with elevated myocardial creatine and creatine kinase (CK) activity. We hypothesised a synergistic effect to augment energetic status, evidenced by an increase in the ratio of phosphocreatine-to-adenosine-triphosphate (PCr/ATP).
Methods and Results: Single transgenic Creatine Transporter overexpressing (CrT-OE, n = 7) and dTg mice (CrT-OE and CK, n = 6) mice were anaesthetised with isoflurane to acquire 31 P-CMRS measurements of the left ventricle (LV) utilising a two-dimensional (2D), threefold under-sampled density-weighted chemical shift imaging (2D-CSI) sequence, which provided high-resolution data with nominal voxel size of 8.5 µl within 70 min. ( 1 H-) cine-CMR data for cardiac function assessment were obtained in the same imaging session. Under a separate examination, mice received invasive haemodynamic assessment, after which tissue was collected for biochemical analysis. Myocardial creatine levels were elevated in all mouse hearts, but only dTg exhibited significantly elevated CK activity, resulting in a 51% higher PCr/ATP ratio in heart (3.01 ± 0.96 vs. 2.04 ± 0.57-mean ± SD; dTg vs. CrT-OE), that was absent from adjacent skeletal muscle. No significant differences were observed for any parameters of LV structure and function, confirming that augmentation of CK activity does not have unforeseen consequences for the heart.
Conclusions: We have developed an improved 31 P-CMRS methodology for the in vivo assessment of energetics in the murine heart which enabled high-resolution imaging within acceptable scan times. Mice over-expressing both creatine and CK in the heart exhibited a synergistic elevation in PCr/ATP that can now be tested for therapeutic potential in models of chronic heart failure.
(© 2023. The Author(s).)
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معلومات مُعتمدة: RE/18/3/34214 BHF Centre of Research Excellence, Oxford; RG/18/12/34040 United Kingdom BHF_ British Heart Foundation; 203141/Z/16/Z United Kingdom WT_ Wellcome Trust; G0600829 United Kingdom MRC_ Medical Research Council; RG/13/8/30266 United Kingdom BHF_ British Heart Foundation; FS/11/50/29038 United Kingdom BHF_ British Heart Foundation
فهرسة مساهمة: Keywords: 31P-CMRS; Creatine kinase; Creatine transporter; Energetics; Metabolism; Myocardial function; Transgenic mice
المشرفين على المادة: EC 2.7.3.2 (Creatine Kinase)
MU72812GK0 (Creatine)
020IUV4N33 (Phosphocreatine)
8L70Q75FXE (Adenosine Triphosphate)
تواريخ الأحداث: Date Created: 20230205 Date Completed: 20230207 Latest Revision: 20240117
رمز التحديث: 20240117
مُعرف محوري في PubMed: PMC9900916
DOI: 10.1186/s12968-023-00911-6
PMID: 36740688
قاعدة البيانات: MEDLINE
الوصف
تدمد:1532-429X
DOI:10.1186/s12968-023-00911-6