Osaka Mizuko, Deushi Michiyo, Aoyama Jiro, Funakoshi Tomoko, Ishigami Akihito, Yoshida Masayuki
Department of Life Science and Bioethics, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
Department of Nutrition and Metabolism in Cardiovascular Disease, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
JACC Basic Transl Sci. 2021 May 19;6(6):507-523. doi: 10.1016/j.jacbts.2021.04.002. eCollection 2021 Jun.
Neutrophil adhesion on the atheroprone femoral artery of high-fat diet-fed low-density lipoprotein receptor-null mice was enhanced more than in wild-type mice. The inhibition of histone H3 citrullination of neutrophils reversed the enhancement of neutrophil adhesion, suggesting that hypercitrullination contributes to enhanced neutrophil adhesion. Furthermore, pemafibrate reduced the citrullination of histone H3 in these mice. Therefore, the hypercitrullination of histone H3 in neutrophils contributes to atherosclerotic vascular inflammation.
与野生型小鼠相比，高脂饮食喂养的低密度脂蛋白受体缺失小鼠的易发生动脉粥样硬化的股动脉上的中性粒细胞黏附增强更为明显。对中性粒细胞组蛋白H3瓜氨酸化的抑制可逆转中性粒细胞黏附的增强，这表明过度瓜氨酸化促进了中性粒细胞黏附增强。此外，匹伐他汀可减少这些小鼠中组蛋白H3的瓜氨酸化。因此，中性粒细胞中组蛋白H3的过度瓜氨酸化会导致动脉粥样硬化性血管炎症。
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