PUBLICATION

Deficiency of heme oxygenase 1a causes detrimental effects on cardiac function

Authors
Wang, H., Siren, J., Perttunen, S., Immonen, K., Chen, Y.C., Narumanchi, S., Kosonen, R., Paavola, J., Laine, M., Tikkanen, I., Lakkisto, P.
ID
ZDB-PUB-240321-8
Date
2024
Source
Journal of Cellular and Molecular Medicine   28: e18243e18243 (Journal)
Registered Authors
Chen, Yu-Chia
Keywords
cardiac hypertrophy, cardiac output, heme oxygenase 1, interstitial fibrosis
MeSH Terms
  • Animals
  • Cardiomyopathies*
  • Heme Oxygenase (Decyclizing)*
  • Heme Oxygenase-1/genetics
  • Humans
  • Hypoxia
  • Isoproterenol/pharmacology
  • Myocardium
  • Myocytes, Cardiac
  • Zebrafish/genetics
(all 10)
PubMed
38509740 Full text @ J. Cell. Mol. Med.
Abstract
Humans lacking heme oxygenase 1 (HMOX1) display growth retardation, haemolytic anaemia, and vulnerability to stress; however, cardiac function remains unclear. We aimed to explore the cardiac function of zebrafish lacking hmox1a at baseline and in response to stress. We generated zebrafish hmox1a mutants using CRISPR/Cas9 genome editing technology. Deletion of hmox1a increases cardiac output and further induces hypertrophy in adults. Adults lacking hmox1a develop myocardial interstitial fibrosis, restrain cardiomyocyte proliferation and downregulate renal haemoglobin and cardiac antioxidative genes. Larvae lacking hmox1a fail to respond to hypoxia, whereas adults are insensitive to isoproterenol stimulation in the heart, suggesting that hmox1a is necessary for cardiac response to stress. Haplodeficiency of hmox1a stimulates non-mitochondrial respiration and cardiac cell proliferation, increases cardiac output in larvae in response to hypoxia, and deteriorates cardiac function and structure in adults upon isoproterenol treatment. Intriguingly, haplodeficiency of hmox1a upregulates cardiac hmox1a and hmox1b in response to isoproterenol. Collectively, deletion of hmox1a results in cardiac remodelling and abrogates cardiac response to hypoxia and isoproterenol. Haplodeficiency of hmox1a aggravates cardiac response to the stress, which could be associated with the upregulation of hmox1a and hmox1b. Our data suggests that HMOX1 homeostasis is essential for maintaining cardiac function and promoting cardioprotective effects.
Genes / Markers
Marker Marker Type Name
epoaGENEerythropoietin a
eporGENEerythropoietin receptor
foxo3aGENEforkhead box O3A
gapdhGENEglyceraldehyde-3-phosphate dehydrogenase
gata1aGENEGATA binding protein 1a
hbaa1GENEhemoglobin, alpha adult 1
hbba1GENEhemoglobin, beta adult 1
hmox1aGENEheme oxygenase 1a
hmox2aGENEheme oxygenase 2a
hmox2bGENEheme oxygenase 2b
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Figures
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Expression
Phenotype
No data available
Mutations / Transgenics
No data available
Human Disease / Model
No data available
Sequence Targeting Reagents
Target Reagent Reagent Type
hmox1aCRISPR5-hmox1aCRISPR
1 - 1 of 1
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Fish
No data available
Antibodies
Orthology
No data available
Engineered Foreign Genes
No data available
Mapping
No data available
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Citation
Wang, H., Siren, J., Perttunen, S., Immonen, K., Chen, Y.C., Narumanchi, S., Kosonen, R., Paavola, J., Laine, M., Tikkanen, I., Lakkisto, P. (2024) Deficiency of heme oxygenase 1a causes detrimental effects on cardiac function. Journal of Cellular and Molecular Medicine. 28:e18243e18243.