Transient Receptor Potential Melastatin 2 Enhances Vascular Reactivity During Development of Atherosclerosis in Mice

Yi-Quan Dai; Xiao-Xiao Yan; Yi-Chen Lin; Hong-Yu Chen; Xiao-Ru Liu

doi:10.1093/ajh/hpaa154

Transient Receptor Potential Melastatin 2 Enhances Vascular Reactivity During Development of Atherosclerosis in Mice

Am J Hypertens. 2021 Feb 18;34(1):121-122. doi: 10.1093/ajh/hpaa154.

Authors

Yi-Quan Dai¹, Xiao-Xiao Yan², Yi-Chen Lin¹, Hong-Yu Chen¹, Xiao-Ru Liu³

Affiliations

¹ Department of Vascular Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China.
² Fujian Children's Hospital, Fuzhou, Fujian, China.
³ Basic Medical School of Fujian Medical University, Fuzhou, Fujian, China.

PMID: 33599748
DOI: 10.1093/ajh/hpaa154

Abstract

Background: To investigate the function of transient receptor potential melastatin 2 (TRPM2) in vascular reactivity induced by 5-hydroxytryptamine (5-HT) in the aorta during development of atherosclerosis in mice.

Methods: Forty mice were randomly divided into 4 groups: C57BL/6J on normal diet (C57 + ND), C57BL/6J on high-fat diet (C57 + HFD), apolipoprotein E gene knockout mice (ApoE-/-) on ND (ApoE-/- + ND), and ApoE-/- on HFD (ApoE-/- + HFD). They were fed with a ND or HFD for 16 weeks. Aortic TRPM2 expression and isometric contractions were analyzed.

Results: In the ApoE-/- + HFD group, body weight, blood glucose, and blood lipid concentrations were increased, and aortic plaques were developed. Compared with the other 3 groups, aortic TRPM2 mRNA and protein levels were significantly increased in the ApoE-/- + HFD group (P < 0.01). Aortic reactivity to 5-HT was enhanced in ApoE-/- + HFD mice with lower EC50 values. The enhanced reactivity to 5-HT was significantly inhibited by TRPM2 inhibitors, N-p-amylcinnamoyl anthranilic acid (1 µmol/l) and 2-aminoethyl diphenylborinate (10 µmol/l).

Conclusions: Aortic TRPM2 expression is upregulated in ApoE knockout mice fed with a HFD. Upregulation of TRPM2 enhances 5-HT vascular reactivity during development of atherosclerosis.