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Transient Receptor Potential Melastatin 2 Enhances Vascular Reactivity During Development of Atherosclerosis in Mice
Yi-Quan Dai1, Xiao-Xiao Yan2, Yi-Chen Lin1
1Department of Vascular Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China.
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.
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