PDSS2 Methylation Exacerbates Heart Failure through Inhibition of the CXCL14/NF-κB Signaling Pathway

Liyan Yu, Shuxia Cai, Xiuli Guo

Article ID: 8026
Vol 38, Issue 5, 2024
DOI: https://doi.org/10.23812/j.biol.regul.homeost.agents.20243805.295
Received: 20 May 2024; Accepted: 20 May 2024; Available online: 20 May 2024; Issue release: 20 May 2024


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Abstract

Background: Numerous reports have suggested a correlation between the occurrence of heart failure (HF) and the methylation status of specific key genes in myocardial cells. This study aimed to elucidate the mechanistic role and functional impact of the methylation of pentenyl diphosphate synthase subunit 2 (PDSS2) methylation in HF, offering insights for novel therapeutic approaches in HF management. Methods: The HF rat model was established via surgical intervention to explore the in vivo exacerbation of HF by PDSS2 methylation. Cardiac ultrasound and morphological assessments were used to evaluate HF in rat hearts. Hematoxylin-eosin (HE) staining was used to assess cardiac injury. The levels of PDSS2 methylation and expression were quantified, and the underlying mechanisms of PDSS2 in HF pathogenesis were explored. Results: Our findings revealed a significant reduction in PDSS2 levels in the heart tissue of HF rats (p < 0.05), concurrent with a notable increase in PDSS2 methylation (p < 0.05). Decreased PDSS2 methylation led to the upregulation of nuclear factor-kappaB (NF-κB) expression (p < 0.05) and chemokine (C-X-C motif) ligand 14 (CXCL14) levels (p < 0.05), consequently attenuating myocardial tissue damage in HF rats. However, silencing CXCL14 or administering the NF-κB inhibitor BAY 11-7082 reversed the protective effects of 5-Aza-2′-deoxycytidine (5-Aza) (p < 0.05), thus increasing myocardial tissue damage in HF rats. Conclusion: PDSS2 methylation is a significant contributor to cardiac dysfunction and the progression to heart failure, underscoring its potential importance in the therapeutic landscape of HF.


Keywords

PDSS2;methylation;NF-κB p65;CXCL14;heart failure


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