Multiomics analysis of right ventricles in rat models of pulmonary arterial hypertension: Consideration of mitochondrial biogenesis by chrysin.
Int J Mol Med
; 49(5)2022 May.
Article
em En
| MEDLINE
| ID: mdl-35315498
ABSTRACT
In pulmonary arterial hypertension (PAH), right ventricular failure is accompanied by metabolic alterations in cardiomyocytes, which may be due to mitochondrial dysfunction and decreased energy production. Chrysin (CH) is a phytochemical with pharmacological activity that is involved in the regulation of mitochondrial biogenesis. The present study investigated the role of CH in the right ventricle (RV) by analyzing the cardiac transcriptome and metabolome of a SU5416(a vascular endothelial growth factor receptor blocker, /hypoxia (Su/Hx) rat model of PAH. RNAsequencing of the RV transcriptome between Su/Hx, Su/Hx with CH (Su/Hx + CH) and control groups, extracellular matrix (ECM) organization and ECMreceptor interactionassociated genes were upregulated in the RV of Su/Hx but not Su/Hx + CH rats. Furthermore, expression of mitochondrial function, energy production, oxidative phosphorylation and tricarboxylic acid (TCA) cycleassociated genes was decreased in the RV of Su/Hx rats; this was reverse by CH. Metabolomic profiling analysis of Su/Hx and Su/Hx + CH rats showed no significant changes in glycolysis, TCA cycle, glutathione, NADH or NADPH. By contrast, in the RV of Su/Hx rats, decreased adenylate energy charge was partially reversed by CH administration, suggesting that CH was involved in the improvement of mitochondrial biogenesis. Reverse transcriptionquantitative PCR analysis revealed that expression of peroxisome proliferatoractivated receptor γ, a master regulator of fatty acid metabolism and mitochondrial biogenesis, was increased in the RV of Su/Hx + CH rats. CH ameliorated cardiac abnormality, including cardiac fibrosis, RV hypertrophy and PH. The present study suggested that CH altered patterns of gene expression and levels of mitochondrial metabolites in cardiomyocytes, thus improving RV dysfunction in a Su/Hx PAH rat model.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Hipertensão Arterial Pulmonar
/
Hipertensão Pulmonar
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article