Targeting Zfp36 to combat cardiac hypertrophy: Insights into ferroptosis pathways

Clinical and Translational Medicine, Journal Year: 2025, Volume and Issue: 15(3)

Published: Feb. 25, 2025

Cardiac hypertrophy is a precursor to heart failure and represents significant global cause of mortality, thereby necessitating timely effective therapeutic interventions. Zinc finger protein 36 (Zfp36) recognised as critical regulator ferroptosis; however, its role underlying mechanisms in cardiac remain largely unexplored. This study aims investigate the regulatory function Zfp36 ferroptosis within context hypertrophy. Single-cell sequencing analysis demonstrated reduction expression associated with was observed mitigate reduce hypertrophic phenotypes cardiomyocytes subjected Angiotensin II (Ang II) myocardial tissues induced by transverse aortic constriction. The inhibitor Ferrostatin-1 shown alleviate when co-incubated si-Zfp36 Ang II. Mechanistically, binds 3' untranslated region (3'UTR) Ythdc2 mRNA, facilitating degradation. subsequently SLC7A11 enhancing decay, which leads glutathione (GSH) levels, exacerbating Furthermore, overexpression reversed protective effects conferred Zfp36, while silencing counteracted knockdown. elucidates hypertrophy, specifically detailing modulatory mechanism via Ythdc2/SLC7A11/GSH pathway. These insights lay groundwork for innovative approaches understanding pathological clinical initially attenuate through inhibition cardiomyocytes, providing new target strategies targeting ferroptosis. facilitated degradation mRNA binding it, inhibiting Ythdc2-mediated maintaining GSH levels. previously unrecognized pathway

Language: Английский

---

Deubiquitinase OTUD7B stabilizes HNF4α to alleviate pressure overload-induced cardiac hypertrophy by regulating fatty acid oxidation and inhibiting ferroptosis

Biomarker Research, Journal Year: 2025, Volume and Issue: 13(1)

Published: March 29, 2025

Abstract Background Cardiac hypertrophy, a leading cause of heart failure, threatens global public health. Deubiquitinating enzymes (DUBs) are critical in cardiac pathophysiology by regulating protein stability, function, and degradation. Here, we investigated the role mechanism ovarian tumor domain-containing 7B (OTUD7B) hypertrophy modulating fatty acid metabolism. Methods Mice subjected to transverse aortic constriction (TAC) cardiomyocytes treated with phenylephrine (PE) were used explore OTUD7B myocardial hypertrophy. The potential molecular mechanisms underlying OTUD7B's regulation explored through transcriptome analysis further validated cardiomyocytes. Results Reduced expression was observed hypertrophic hearts following TAC surgery. Cardiac-specific deficiency exacerbated, while overexpression mitigated, pressure overload-induced dysfunction both vivo vitro. knockdown resulted ferroptosis, as evidenced decreased mitochondrial cristae, increased Fe 2+ ion content, lipid peroxide accumulation, inhibited ferroptosis. Mechanistically, transcriptomic identified plays metabolism pathological found directly bind HNF4α, transcription factor oxidation-related genes. Further, exerted deubiquitination activity stabilize HNF4α removing K48-linked ubiquitin chains, thereby preventing its degradation via proteasomal pathway linking Finally, ferroptosis inhibitors, ferrostatin-1, alleviated inhibition-induced suppression, Conclusions We confirmed that is involved highlighted alleviates oxidation stabilization HNF4α.

Language: Английский

---

Gut microbiome and inflammation in cardiovascular drug response: trends in therapeutic success and commercial focus

Inflammopharmacology, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 2, 2024

Language: Английский

---

What is the link between ferroptosis and cardiac hypertrophy?

Canadian Journal of Cardiology, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 1, 2024

Language: Английский

---