S100A9 deficiency mitigates cardiac oxidative stress and improves function via SIRT3 in HFpEF mice
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Le résumé fourni par la source
Heart failure with preserved ejection fraction (HFpEF) is the predominant manifestation of heart failure, yet effective treatment options remain limited, and its underlying mechanisms are not well understood. In the present study, the hearts of HFpEF mice were collected for proteomics analyses, and differentially expressed proteins were screened. Then, the effects of S100A9 on HFpEF were investigated using S100A9-knockout (KO) mice. The results revealed elevated levels of S100A8 and S100A9 mRNA and protein in the hearts of HFpEF mice, primarily driven by high-fat diet (HFD) exposure. S100A9 deficiency resulted in lowered systolic blood pressure, reduced cardiac oxidative stress, enhanced mitochondrial bioenergetics, mitigated myocardial hypertrophy and fibrosis, ultimately improving cardiac diastolic dysfunction and alleviating pulmonary congestion in HFpEF mice. Moreover, S100A9 deficiency increased the NAD + /NADH ratio, restored SIRT3 levels, decreased NOX2 expression, and suppressed the hyperacetylation of SOD2 at its K68 site in HFpEF hearts. Inhibiting SIRT3 diminished the protective effects of S100A9 deficiency on cardiac diastolic dysfunction in vivo . In vitro , palmitic acid (PA) significantly elevated S100A8 and S100A9 expression in cardiomyocytes via oxidative stress-related mechanisms. Recombinant mouse S100A9 protein decreased SIRT3 expression, leading to oxidative stress and mitochondrial dysfunction. S100A9 knockdown mitigated PA-induced oxidative stress and mitochondrial dysfunction by preserving SIRT3 expression. In conclusion, our study suggests that S100A9 deficiency improves cardiac function by reducing oxidative stress and alleviating mitochondrial dysfunction through increasing SIRT3 levels in HFpEF mice.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- S100A9 deficiency mitigates cardiac oxidative stress and improves function via SIRT3 in HFpEF mice
- Date Crossref
- 01/02/2026
- Éditeur
- Elsevier BV
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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The Affiliated Yongchuan Hospital of Chongqing Medical University Department of Cardiovascular Medicine pays non établi dans la noticeÉtablissement de santé
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Chongqing Science and Technology Commission pays non établi dans la noticeOrganisme public
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Chongqing Medical University Department of Cardiovascular Medicine pays non établi dans la noticeUniversité ou école supérieure
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Chongqing Three Gorges Central Hospital pays non établi dans la noticeÉtablissement de santé
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Chongqing Three Gorges University pays non établi dans la noticeUniversité ou école supérieure
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Key Laboratory of Circulatory System Stress and Disease of Chongqing Municipal Education Commission pays non établi dans la noticeStructure de recherche
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The First Affiliated Hospital of Chongqing University Department of Nephrology pays non établi dans la noticeUniversité ou école supérieure
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Chongqing University Three Gorges Hospital Department of Cardiovascular Medicine pays non établi dans la noticeUniversité ou école supérieure
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School of Basic Medical Sciences pays non établi dans la noticeUniversité ou école supérieure
Department of Cardiovascular Medicine — The Affiliated Yongchuan Hospital of Chongqing Medical University, Chongqing Science and Technology Commission et Department of Cardiovascular Medicine — Chongqing Medical University, avec 6 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.