HIF-1α limits myocardial infarction by promoting mitophagy in mouse hearts adapted to chronic hypoxia
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985823%3A_____%2F24%3A00598395" target="_blank" >RIV/67985823:_____/24:00598395 - isvavai.cz</a>
Alternative codes found
RIV/86652036:_____/24:00598395 RIV/00216208:11310/24:10497601
Result on the web
<a href="https://doi.org/10.1111/apha.14202" target="_blank" >https://doi.org/10.1111/apha.14202</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1111/apha.14202" target="_blank" >10.1111/apha.14202</a>
Alternative languages
Result language
angličtina
Original language name
HIF-1α limits myocardial infarction by promoting mitophagy in mouse hearts adapted to chronic hypoxia
Original language description
Aim: The transcriptional factor HIF-1α is recognized for its contribution to cardioprotection against acute ischemia/reperfusion injury. Adaptation to chronic hypoxia (CH) is known to stabilize HIF-1α and increase myocardial ischemic tolerance. However, the precise role of HIF-1α in mediating the protective effect remains incompletely understood. Methods: Male wild-type (WT) mice and mice with partial Hif1a deficiency (hif1a+/−) were exposed to CH for 4 weeks, while their respective controls were kept under normoxic conditions. Subsequently, their isolated perfused hearts were subjected to ischemia/reperfusion to determine infarct size, while RNA-sequencing of isolated cardiomyocytes was performed. Mitochondrial respiration was measured to evaluate mitochondrial function, and western blots were performed to assess mitophagy. Results: We demonstrated enhanced ischemic tolerance in WT mice induced by adaptation to CH compared with their normoxic controls and chronically hypoxic hif1a+/− mice. Through cardiomyocyte bulk mRNA sequencing analysis, we unveiled significant reprogramming of cardiomyocytes induced by CH emphasizing mitochondrial processes. CH reduced mitochondrial content and respiration and altered mitochondrial ultrastructure. Notably, the reduced mitochondrial content correlated with enhanced autophagosome formation exclusively in chronically hypoxic WT mice, supported by an increase in the LC3-II/LC3-I ratio, expression of PINK1, and degradation of SQSTM1/p62. Furthermore, pretreatment with the mitochondrial division inhibitor (mdivi-1) abolished the infarct size-limiting effect of CH in WT mice, highlighting the key role of mitophagy in CH-induced cardioprotection. Conclusion: These findings provide new insights into the contribution of HIF-1α to cardiomyocyte survival during acute ischemia/reperfusion injury by activating the selective autophagy pathway.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30201 - Cardiac and Cardiovascular systems
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2024
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Acta Physiologica
ISSN
1748-1708
e-ISSN
1748-1716
Volume of the periodical
240
Issue of the periodical within the volume
9
Country of publishing house
US - UNITED STATES
Number of pages
18
Pages from-to
e14202
UT code for WoS article
001270133000001
EID of the result in the Scopus database
2-s2.0-85198735524