Application of 4-D ultrasound-derived regional strain and proteomics analysis in

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JMG, Male, Animals, Mice, Cross-Sectional Studies, Proteomics, Ultrasonography, Ventricular Dysfunction, Left, Cardiomyopathies, Homeobox Protein Nkx-2.5

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Am J Physiol Heart Circ Physiol. 2023;325(2):H293-H310







This work was supported by American Heart Association Grant 14SDG18220010 (to C.J.G.), National Institutes of Health Grants F30-HL145980 (to F.W.D.) and T32-DK101001 (to C.J.G.), a Purdue University/Jackson Laboratories incentive pilot grant (to M.W.C. and C.J.G.), and the Geddes Endowment from Purdue University (to C.J.G.).


The comprehensive characterization of cardiac structure and function is critical to better understanding various murine models of cardiac disease. We demonstrate here a multimodal analysis approach using high-frequency four-dimensional ultrasound (4DUS) imaging and proteomics to explore the relationship between regional function and tissue composition in a murine model of metabolic cardiomyopathy (Nkx2-5183P/ þ ). The presented 4DUS analysis outlines a novel approach to mapping both circumfer- ential and longitudinal strain profiles through a standardized framework. We then demonstrate how this approach allows for spa- tiotemporal comparisons of cardiac function and improved localization of regional left ventricular dysfunction. Guided by observed trends in regional dysfunction, our targeted Ingenuity Pathway Analysis (IPA) results highlight metabolic dysregulation in the Nkx2-5183P/ þ model, including altered mitochondrial function and energy metabolism (i.e., oxidative phosphorylation and fatty acid/lipid handling). Finally, we present a combined 4DUS-proteomics z-score-based analysis that highlights IPA canonical pathways showing strong linear relationships with 4DUS biomarkers of regional cardiac dysfunction. The presented multimodal analysis methods aim to help future studies more comprehensively assess regional structure-function relationships in other pre- clinical models of cardiomyopathy.