Abstract

Both exercise-induced molecular mechanisms and physiological cardiac remodeling have been previously studied on a whole heart level. However, the regional microstructural tissue effects of these molecular mechanisms in the heart have yet to be spatially linked and further elucidated. We show in exercised mice that the expression of CITED4, a transcriptional co-regulator necessary for cardioprotection, is regionally heterogenous in the heart with preferential significant increases in the lateral wall compared with sedentary mice. Concordantly in this same region, the heart’s local microstructural tissue helicity is also selectively increased in exercised mice. Quantification of CITED4 expression and microstructural tissue helicity reveals a significant correlation across both sedentary and exercise mouse cohorts. Furthermore, genetic deletion of CITED4 in the heart prohibits regional exercise-induced microstructural helicity remodeling. Taken together, CITED4 expression is necessary for exercise-induced regional remodeling of the heart’s microstructural helicity revealing how a key molecular regulator of cardiac remodeling manifests into downstream local tissue-level changes.

Expression of transcription factor CITED4 is necessary for exercise-induced regional remodeling of the heart’s microstructural helicity, revealing how a key molecular regulator of cardiac remodeling mediates local tissue-level changes.

Details

Title
Exercise-induced CITED4 expression is necessary for regional remodeling of cardiac microstructural tissue helicity
Author
Eder, Robert A. 1   VIAFID ORCID Logo  ; van den Boomen, Maaike 2   VIAFID ORCID Logo  ; Yurista, Salva R. 3   VIAFID ORCID Logo  ; Rodriguez-Aviles, Yaiel G. 4   VIAFID ORCID Logo  ; Islam, Mohammad Rashedul 3 ; Chen, Yin-Ching Iris 5 ; Trager, Lena 1 ; Coll-Font, Jaume 6 ; Cheng, Leo 5 ; Li, Haobo 3   VIAFID ORCID Logo  ; Rosenzweig, Anthony 7   VIAFID ORCID Logo  ; Wrann, Christiane D. 8   VIAFID ORCID Logo  ; Nguyen, Christopher T. 9   VIAFID ORCID Logo 

1  Massachusetts General Hospital, Cardiovascular Research Center, Charlestown, USA (GRID:grid.32224.35) (ISNI:0000 0004 0386 9924) 
2  Massachusetts General Hospital, Cardiovascular Research Center, Charlestown, USA (GRID:grid.32224.35) (ISNI:0000 0004 0386 9924); Massachusetts General Hospital, Martinos Center for Biomedical Imaging, Charlestown, USA (GRID:grid.32224.35) (ISNI:0000 0004 0386 9924); University Medical Center Groningen, University of Groningen, Department of Radiology, Groningen, The Netherlands (GRID:grid.4494.d) (ISNI:0000 0000 9558 4598); Harvard Medical School, Boston, USA (GRID:grid.38142.3c) (ISNI:000000041936754X) 
3  Massachusetts General Hospital, Cardiovascular Research Center, Charlestown, USA (GRID:grid.32224.35) (ISNI:0000 0004 0386 9924); Harvard Medical School, Boston, USA (GRID:grid.38142.3c) (ISNI:000000041936754X) 
4  Massachusetts General Hospital, Cardiovascular Research Center, Charlestown, USA (GRID:grid.32224.35) (ISNI:0000 0004 0386 9924); Ponce Health Sciences University, School of Medicine, Ponce, USA (GRID:grid.262009.f) (ISNI:0000 0004 0455 6268) 
5  Massachusetts General Hospital, Martinos Center for Biomedical Imaging, Charlestown, USA (GRID:grid.32224.35) (ISNI:0000 0004 0386 9924); Harvard Medical School, Boston, USA (GRID:grid.38142.3c) (ISNI:000000041936754X) 
6  Massachusetts General Hospital, Cardiovascular Research Center, Charlestown, USA (GRID:grid.32224.35) (ISNI:0000 0004 0386 9924); Massachusetts General Hospital, Martinos Center for Biomedical Imaging, Charlestown, USA (GRID:grid.32224.35) (ISNI:0000 0004 0386 9924); Harvard Medical School, Boston, USA (GRID:grid.38142.3c) (ISNI:000000041936754X) 
7  Massachusetts General Hospital, Cardiovascular Research Center, Charlestown, USA (GRID:grid.32224.35) (ISNI:0000 0004 0386 9924); Harvard Medical School, Boston, USA (GRID:grid.38142.3c) (ISNI:000000041936754X); Massachusetts General Hospital, Cardiology Division and Corrigan Minehan Heart Center, Boston, USA (GRID:grid.32224.35) (ISNI:0000 0004 0386 9924) 
8  Massachusetts General Hospital, Cardiovascular Research Center, Charlestown, USA (GRID:grid.32224.35) (ISNI:0000 0004 0386 9924); Harvard Medical School, Boston, USA (GRID:grid.38142.3c) (ISNI:000000041936754X); McCance Center for Brain Health, Massachusetts General Hospital, Boston, USA (GRID:grid.32224.35) (ISNI:0000 0004 0386 9924) 
9  Massachusetts General Hospital, Cardiovascular Research Center, Charlestown, USA (GRID:grid.32224.35) (ISNI:0000 0004 0386 9924); Massachusetts General Hospital, Martinos Center for Biomedical Imaging, Charlestown, USA (GRID:grid.32224.35) (ISNI:0000 0004 0386 9924); Harvard Medical School, Boston, USA (GRID:grid.38142.3c) (ISNI:000000041936754X); Harvard-Massachusetts Institute of Technology, Division of Health Sciences and Technology, Cambridge, USA (GRID:grid.116068.8) (ISNI:0000 0001 2341 2786); Cleveland Clinic, Cleveland, Cardiovascular Innovation Research Center, Heart, Vascular, and Thoracic Institute, Ohio, USA (GRID:grid.239578.2) (ISNI:0000 0001 0675 4725) 
Publication year
2022
Publication date
2022
Publisher
Nature Publishing Group
e-ISSN
23993642
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s42003-022-03635-y
ProQuest document ID
2684318986
Copyright
© The Author(s) 2022. corrected publication 2022. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.