2. Academic Validation
  3. Vitamin C alleviates LPS-induced myocardial injury by inhibiting pyroptosis via the ROS-AKT/mTOR signalling pathway

Vitamin C alleviates LPS-induced myocardial injury by inhibiting pyroptosis via the ROS-AKT/mTOR signalling pathway

  • BMC Cardiovasc Disord. 2022 Dec 22;22(1):561. doi: 10.1186/s12872-022-03014-9.
Pu Zhang 1 2,  Meirong Zang 3,  Zhenzhen Sang 1,  Yunxia Wei 1,  Yan Yan 1,  Xiaohua Bian 1,  Shimin Dong 4
Affiliations

Affiliations

  • 1 Department of Emergency, The Third Hospital of Hebei Medical University, Zi-Qiang Road No. 139, Shijiazhuang, 050051, Hebei, China.
  • 2 Department of Otolaryngology, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
  • 3 Department of Haematology, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
  • 4 Department of Emergency, The Third Hospital of Hebei Medical University, Zi-Qiang Road No. 139, Shijiazhuang, 050051, Hebei, China. [email protected].
PMID: 36550401 DOI: 10.1186/s12872-022-03014-9
Abstract

Background: The efficacy of vitamin C in sepsis remains controversial. Whether vitamin C can alleviate lipopolysaccharide (LPS)-induced myocardial injury by inhibiting Pyroptosis has not been studied. This study aimed to evaluate the effects of vitamin C on LPS-induced myocardial injury in vitro.

Methods: H9C2 cells were treated with indicated concentrations of LPS, and the cell viability was then assessed by CCK-8 assay. The levels of Lactate Dehydrogenase (LDH), CK-MB, IL-18 and IL-1β were examined by enzyme-linked immunosorbent assay (ELISA). The levels of intracellular Reactive Oxygen Species (ROS) were measured using the fluorescent probe dichlorodihydrofluorescein diacetate (DCFH-DA). Western blot assays were conducted to determine the levels of the ROS-associated protein nicotinamide adenine dinucleotide phosphate oxidase 4 (Nox4) and pyroptosis-associated proteins, such as NOD-like receptor (NLR) family pyrin domain containing 3 (NLRP3), Caspase-1 and gasdermin D (GSDMD). The Akt Inhibitor MK-2206 was then applied to explore the signalling pathway. Finally, H9C2 cells were divided into the control group, LPS group, vitamin C + LPS group, and N-acetyl-L-cysteine (NAC) + LPS group. The intracellular ROS, levels of associated proteins, cell viability, and release of LDH, CK-MB, IL-18 and IL-1β were examined.

Results: LPS decreased cell viability and induced ROS and Pyroptosis in H9C2 cells in a dose-dependent manner. Moreover, LPS activated the Akt/mTOR pathway in H9C2 cells. The Akt Inhibitor MK-2206 protected H9C2 cells from LPS-induced death by suppressing Pyroptosis, without changing intracellular ROS level. Vitamin C significantly inhibited intracellular ROS and cell Pyroptosis in LPS-treated H9C2 cells. Moreover, vitamin C suppressed the activation of the Akt/mTOR pathway.

Conclusions: Our data suggest that vitamin C alleviates LPS-induced myocardial injury by inhibiting Pyroptosis via the ROS-AKT/mTOR signalling pathway and thus provide novel insights into the prevention of sepsis-induced myocardial dysfunction.

Keywords

Myocardial injury; Pyroptosis; Reactive oxygen species (ROS); Sepsis; Vitamin C.

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