Počet záznamů: 1
HIF-1α limits myocardial infarction by promoting mitophagy in mouse hearts adapted to chronic hypoxia
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SYSNO ASEP 0598395 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název HIF-1α limits myocardial infarction by promoting mitophagy in mouse hearts adapted to chronic hypoxia Tvůrce(i) Alánová, Petra (FGU-C) RID, ORCID
Alán, Lukáš (FGU-C) RID, ORCID
Opletalová, Barbora (FGU-C) RID, ORCID
Bohuslavová, Romana (BTO-N) RID
Abaffy, Pavel (BTO-N) ORCID, RID
Matějková, Kateřina (BTO-N)
Holzerová, Kristýna (FGU-C) ORCID, RID
Benák, Daniel (FGU-C) ORCID, RID
Kaludercic, N. (IT)
Menabo, R. (IT)
Di Lisa, F. (IT)
Ošťádal, Bohuslav (FGU-C) RID, ORCID
Kolář, František (FGU-C) RID, ORCID, SAI
Pavlínková, Gabriela (BTO-N) RID, ORCIDČíslo článku e14202 Zdroj.dok. Acta Physiologica. - : Wiley - ISSN 1748-1708
Roč. 240, č. 9 (2024)Poč.str. 18 s. Jazyk dok. eng - angličtina Země vyd. US - Spojené státy americké Klíč. slova cardioprotection ; chronic hypoxia ; hypoxia-inducible factor 1 alpha ; mitochondria ; mitophagy ; myocardial infarction Obor OECD Cardiac and Cardiovascular systems CEP LX22NPO5104 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy NU20J-02-00035 GA MZd - Ministerstvo zdravotnictví Výzkumná infrastruktura CCP II - 90126 - Ústav molekulární genetiky AV ČR, v. v. i. Způsob publikování Open access Institucionální podpora FGU-C - RVO:67985823 ; BTO-N - RVO:86652036 UT WOS 001270133000001 EID SCOPUS 85198735524 DOI https://doi.org/10.1111/apha.14202 Anotace 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. Pracoviště Fyziologický ústav Kontakt Lucie Trajhanová, lucie.trajhanova@fgu.cas.cz, Tel.: 241 062 400 Rok sběru 2025 Elektronická adresa https://doi.org/10.1111/apha.14202
Počet záznamů: 1