2. Academic Validation
  3. NLRX1 attenuates endoplasmic reticulum stress via STING in cardiac hypertrophy

NLRX1 attenuates endoplasmic reticulum stress via STING in cardiac hypertrophy

  • Biochim Biophys Acta Mol Cell Res. 2024 Dec;1871(8):119852. doi: 10.1016/j.bbamcr.2024.119852.
Keying Mi 1,  Xiaoyan Wang 1,  Chao Ma 2,  Yinghua Tan 2,  Gang Zhao 3,  Xinran Cao 4,  Haitao Yuan 5
Affiliations

Affiliations

  • 1 Department of Cardiology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong 250021, People's Republic of China; JiNan Key Laboratory of Cardiovascular Disease, Jinan, China.
  • 2 Department of Cardiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, People's Republic of China; JiNan Key Laboratory of Cardiovascular Disease, Jinan, China.
  • 3 Department of Cardiology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong 250021, People's Republic of China; Department of Cardiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, People's Republic of China; JiNan Key Laboratory of Cardiovascular Disease, Jinan, China.
  • 4 Department of Cardiology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong 250021, People's Republic of China; Department of Cardiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, People's Republic of China; JiNan Key Laboratory of Cardiovascular Disease, Jinan, China. Electronic address: caoxinran@sdfmu.edu.cn.
  • 5 Department of Cardiology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong 250021, People's Republic of China; Department of Cardiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, People's Republic of China; JiNan Key Laboratory of Cardiovascular Disease, Jinan, China. Electronic address: yuanhaitao@sdfmu.edu.cn.
PMID: 39357547 DOI: 10.1016/j.bbamcr.2024.119852
Abstract

Endoplasmic reticulum stress-induced cell Apoptosis is a pivotal mechanism underlying the progression of cardiac hypertrophy. NLRX1, a member of the NOD-like Receptor family, modulates various cellular processes, including STING, NF-κB, MAPK pathways, Reactive Oxygen Species production, essential metabolic pathways, Autophagy and cell death. Emerging evidence suggests that NLRX1 may offer protection against diverse cardiac diseases. However, the impacts and mechanisms of NLRX1 on endoplasmic reticulum stress in cardiac hypertrophy remains largely unexplored. In our study, we observed that the NLRX1 and phosphorylated STING (p-STING) were highly expressed in both hypertrophic mouse heart and cellular model of cardiac hypertrophy. Whereas over-expression of NLRX1 mitigated the expression levels of p-STING, as well as the endoplasmic reticulum stress markers, including transcription activating factor 4 (ATF4), C/EBP homologous protein (CHOP) and the ratios of phosphorylated PERK to PERK, phosphorylated IRE1 to IRE1 and phosphorylated eIF2α to eIF2α in an Angiotensin II (Ang II)-induced cellular model of cardiac hypertrophy. Importantly, the protective effects of NLRX1 were attenuated upon pretreatment with the STING agonist, DMXAA. Our findings provide the evidence that NLRX1 attenuates the PERK-eIF2α-ATF4-CHOP axis of endoplasmic reticulum stress response via inhibition of p-STING in Ang II-treated cardiomyocytes, thereby ameliorating the development of cardiac hypertrophy.

Keywords

Cardiac hypertrophy; Endoplasmic reticulum stress; NLRX1; STING.

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