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Quast 2022 Basic Res Cardiol

From Bioblast
Publications in the MiPMap
Quast C, Kober F, Becker K, Zweck E, Hoffe J, Jacoby C, Flocke V, Gyamfi-Poku I, Keyser F, Piayda K, Erkens R, Niepmann S, Adam M, Baldus S, Zimmer S, Nickenig G, Grandoch M, Bönner F, Kelm M, Flögel U (2022) Multiparametric MRI identifies subtle adaptations for demarcation of disease transition in murine aortic valve stenosis.

» Basic Res Cardiol 117:29. PMID: 35643805 Open Access

Quast Christine,  Kober Frank, Becker Katrin, Zweck Elric, Hoffe Jasmina,  Jacoby Christoph,  Flocke Vera,  Gyamfi-Poku Isabella,  Keyser Fabian,  Piayda Kerstin,  Erkens Ralf,  Niepmann Sven,  Adam Matti,  Baldus Stephan, Zimmer Sebastian,  Nickenig Georg, Grandoch Maria,  Boenner Florian,  Kelm Malte,  Floegel Ulrich (2022) Basic Res Cardiol

Abstract: Aortic valve stenosis (AS) is the most frequent valve disease with relevant prognostic impact. Experimental model systems for AS are scarce and comprehensive imaging techniques to simultaneously quantify function and morphology in disease progression are lacking. Therefore, we refined an acute murine AS model to closely mimic human disease characteristics and developed a high-resolution magnetic resonance imaging (MRI) approach for simultaneous in-depth analysis of valvular, myocardial as well as aortic morphology/pathophysiology to identify early changes in tissue texture and critical transition points in the adaptive process to AS. AS was induced by wire injury of the aortic valve. Four weeks after surgery, cine loops, velocity, and relaxometry maps were acquired at 9.4 T to monitor structural/functional alterations in valve, aorta, and left ventricle (LV). In vivo MRI data were subsequently validated by histology and compared to echocardiography. AS mice exhibited impaired valve opening accompanied by significant valve thickening due to fibrotic remodelling. While control mice showed bell-shaped flow profiles, AS resulted not only in higher peak flow velocities, but also in fragmented turbulent flow patterns associated with enhanced circumferential strain and an increase in wall thickness of the aortic root. AS mice presented with a mild hypertrophy but unaffected global LV function. Cardiac MR relaxometry revealed reduced values for both T1 and T2 in AS reflecting subtle myocardial tissue remodelling with early alterations in mitochondrial function in response to the enhanced afterload. Concomitantly, incipient impairments of coronary flow reserve and myocardial tissue integrity get apparent accompanied by early troponin release. With this, we identified a premature transition point with still compensated cardiac function but beginning textural changes. This will allow interventional studies to explore early disease pathophysiology and novel therapeutic targets. Keywords: Aortic flow patterns, Aortic valve stenosis, MRI, Tissue characterization, Vessel wall remodelling Bioblast editor: Plangger M

Labels: MiParea: Respiration  Pathology: Cardiovascular 

Organism: Mouse  Tissue;cell: Heart  Preparation: Permeabilized tissue 

Coupling state: LEAK, OXPHOS, ET  Pathway: F, N, S, NS, ROX  HRR: Oxygraph-2k