The Degree of Cardiac Remodelling before Overload Relief Triggers Different Transcriptome and miRome Signatures during Reverse Remodelling (RR)—Molecular Signature Differ with the Extent of RR

Autor: Adelino F. Leite-Moreira, Inês Falcão-Pires, Daniela Miranda-Silva, Ralph Knöll, Cláudia Sousa-Mendes, Ricardo Martins-Ferreira, Xidan Li, Patrícia Rodrigues, Zaher Elbeck
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Male
0301 basic medicine
Cardiac function curve
medicine.medical_specialty
reverse remodelling
Diastole
Hemodynamics
030204 cardiovascular system & hematology
Article
Catalysis
Muscle hypertrophy
lcsh:Chemistry
Inorganic Chemistry
myocardial metabolism
Mice
03 medical and health sciences
0302 clinical medicine
Fibrosis
Internal medicine
medicine
Animals
Myocytes
Cardiac
Physical and Theoretical Chemistry
lcsh:QH301-705.5
Molecular Biology
Spectroscopy
Pressure overload
Ventricular Remodeling
business.industry
Organic Chemistry
fibrosis
General Medicine
medicine.disease
Computer Science Applications
Mice
Inbred C57BL
MicroRNAs
030104 developmental biology
medicine.anatomical_structure
lcsh:Biology (General)
lcsh:QD1-999
Ventricle
Cardiology
pressure-overload
Hypertrophy
Left Ventricular
Myocardial fibrosis
diastolic dysfunction
Transcriptome
business
Zdroj: International Journal of Molecular Sciences
Volume 21
Issue 24
International Journal of Molecular Sciences, Vol 21, Iss 9687, p 9687 (2020)
ISSN: 1422-0067
DOI: 10.3390/ijms21249687
Popis: This study aims to provide new insights into transcriptome and miRome modifications occurring in cardiac reverse remodelling (RR) upon left ventricle pressure-overload relief in mice. Pressure-overload was established in seven-week-old C57BL/6J-mice by ascending aortic constriction. A debanding (DEB) surgery was performed seven weeks later in half of the banding group (BA). Two weeks later, cardiac function was evaluated through hemodynamics and echocardiography, and the hearts were collected for histology and small/bulk-RNA-sequencing. Pressure-overload relief was confirmed by the normalization of left-ventricle-end-systolic-pressure. DEB animals were separated into two subgroups according to the extent of cardiac remodelling at seven weeks and RR: DEB1 showed an incomplete RR phenotype confirmed by diastolic dysfunction persistence (E/e&rsquo
&ge
16 ms) and increased myocardial fibrosis. At the same time, DEB2 exhibited normal diastolic function and fibrosis, presenting a phenotype closer to myocardial recovery. Nevertheless, both subgroups showed the persistence of cardiomyocytes hypertrophy. Notably, the DEB1 subgroup presented a more severe diastolic dysfunction at the moment of debanding than the DEB2, suggesting a different degree of cardiac remodelling. Transcriptomic and miRomic data, as well as their integrated analysis, revealed significant downregulation in metabolic and hypertrophic related pathways in DEB1 when compared to DEB2 group, including fatty acid &beta
oxidation, mitochondria L-carnitine shuttle, and nuclear factor of activated T-cells pathways. Moreover, extracellular matrix remodelling, glycan metabolism and inflammation-related pathways were up-regulated in DEB1. The presence of a more severe diastolic dysfunction at the moment of pressure overload-relief on top of cardiac hypertrophy was associated with an incomplete RR. Our transcriptomic approach suggests that a cardiac inflammation, fibrosis, and metabolic-related gene expression dysregulation underlies diastolic dysfunction persistence after pressure-overload relief, despite left ventricular mass regression, as echocardiographically confirmed.
Databáze: OpenAIRE
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