NLRP3 inflammasome contributes to endothelial dysfunction in angiotensin II-induced hypertension in mice

  • Microvasc Res. 2022 Sep;143:104384. doi: 10.1016/j.mvr.2022.104384.
Xingbing Li  1 ,  Ziyue Zhang  2 ,  Minghao Luo  1 ,  Zhe Cheng  1 ,  Ruiyu Wang  1 ,  Qian Liu  1 ,  Dingyi Lv  1 ,  Jianghong Yan  3 ,  Feifei Shang  3 ,  Suxin Luo  4 ,  Yong Xia  5
Affiliations
  • 1. Department of Cardiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, PR China; Institute of Life Sciences, Chongqing Medical University, Chongqing, PR China.
  • 2. Department of Cardiology, Daping Hospital, Army Medical University, Chongqing, PR China; Chongqing Key Laboratory for Hypertension Research, Chongqing Cardiovascular Clinical Research Center, Chongqing Institute of Cardiology, Chongqing, PR China.
  • 3. Institute of Life Sciences, Chongqing Medical University, Chongqing, PR China.
  • 4. Department of Cardiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, PR China; Institute of Life Sciences, Chongqing Medical University, Chongqing, PR China. Electronic address: [email protected].
  • 5. Department of Cardiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, PR China; Institute of Life Sciences, Chongqing Medical University, Chongqing, PR China; Davis Heart & Lung Research Institute, The Ohio State University College of Medicine, Columbus, OH, USA. Electronic address: [email protected].
PMID: 35618036 DOI: 10.1016/j.mvr.2022.104384
Abstract

Aims: Inflammation is a key feature of endothelial dysfunction induced by angiotensin (Ang) II. The purpose of this study was to explore the role of Nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome in endothelial dysfunction in Ang II-induced hypertension.

Materials and methods: We analyzed blood pressure and vascular function of wild-type (WT) and NLRP3 knockout (NLRP3-/-) mice, treated with Ang II. In vitro, we mainly tested the endothelial nitric oxide synthase (eNOS) phosphorylation expression of human umbilical vein endothelial cells (HUVECs).

Key findings: Here we showed that 14-day Ang II infusion into mice resulted in the elevation of blood pressure, NLRP3 expression, serum interleukin (IL)-1β level, and the decline of endothelium-dependent relaxation function, p-eNOS-Ser1177 expression in aortas. NLRP3 deficiency reduced Ang II-induced blood pressure elevation and endothelial dysfunction. In vitro, NLRP3 was involved in the effect of Ang II on reducing p-eNOS-Ser1177 expression. Moreover, the direct effect of IL-1β on vascular endothelial injury could be observed in both vivo and vitro.

Significance: Our result demonstrates that the NLRP3 inflammasome is critically involved in the detrimental effects of Ang II on vascular endothelium in hypertension via the activation of IL-1β, placing NLRP3 as a potential target for therapeutic interventions in conditions with endothelial dysfunction in hypertension.

Keywords
Angiotensin II; Endothelial dysfunction; Hypertension; NLRP3; eNOS.
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