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Of Mouse and Man: Cross-Species Characterization of Hypertensive Cardiac Remodeling

Cooper, STE; Westaby, JD; Haines, ZHR; Malone, GO; Sheppard, MN; Meijles, DN (2022) Of Mouse and Man: Cross-Species Characterization of Hypertensive Cardiac Remodeling. International Journal of Molecular Sciences, 23 (14). p. 7709. ISSN 1422-0067 https://doi.org/10.3390/ijms23147709
SGUL Authors: Westaby, Joseph David Sheppard, Mary Noelle Meijles, Daniel Nathan

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Abstract

Hypertension is a major public health concern and poses a significant risk for sudden cardiac death (SCD). However, the characterisation of human tissues tends to be macroscopic, with little appreciation for the quantification of the pathological remodelling responsible for the advancement of the disease. While the components of hypertensive remodelling are well established, the timeline and comparative quantification of pathological changes in hypertension have not been shown before. Here, we sought to identify the phasing of cardiac remodelling with hypertension using post-mortem tissue from SCD patients with early and advanced hypertensive heart disease (HHD). In order to study and quantify the progression of phenotypic changes, human specimens were contrasted to a well-described angiotensin-II-mediated hypertensive mouse model. While cardiomyocyte hypertrophy is an early adaptive response in the mouse that stabilises in established hypertension and declines as the disease progresses, this finding did not translate to the human setting. In contrast, optimising fibrosis quantification methods and applying them to each setting identified perivascular fibrosis as the prevailing possible cause for overall disease progression. Indeed, assessing myocardial inflammation highlights CD45+ inflammatory cell infiltration that precedes fibrosis and is an early-phase event in response to elevated arterial pressures that may underscore perivascular remodelling. Along with aetiology insight, we highlight cross-species comparison for quantification of cardiac remodelling in human hypertension. As such, this platform could assist with the development of therapies specific to the disease phase rather than targeting global components of hypertension, such as blood pressure lowering.

Item Type: Article
Additional Information: Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Keywords: 0399 Other Chemical Sciences, 0604 Genetics, 0699 Other Biological Sciences, Chemical Physics
SGUL Research Institute / Research Centre: Academic Structure > Molecular and Clinical Sciences Research Institute (MCS)
Journal or Publication Title: International Journal of Molecular Sciences
ISSN: 1422-0067
Language: en
Dates:
DateEvent
12 July 2022Published
5 July 2022Accepted
Publisher License: Creative Commons: Attribution 4.0
Projects:
Project IDFunderFunder ID
FS/19/24/34262British Heart Foundationhttp://dx.doi.org/10.13039/501100000274
URI: https://openaccess.sgul.ac.uk/id/eprint/114566
Publisher's version: https://doi.org/10.3390/ijms23147709

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