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肽聚糖识别蛋白 1 通过抑制内皮细胞黏附来减轻动脉粥样硬化。

Peptidoglycan Recognition Protein 1 Attenuates Atherosclerosis by Suppressing Endothelial Cell Adhesion.

机构信息

Department of Cardiology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China .

Y. Jin and H. Huang contributed equally to the work.

出版信息

J Cardiovasc Pharmacol. 2021 Oct 1;78(4):615-621. doi: 10.1097/FJC.0000000000001100.

DOI:10.1097/FJC.0000000000001100
PMID:34269701
Abstract

Peptidoglycan recognition protein 1 (PGLYRP1) has long been believed to play an important role in infectious and immune diseases. We hypothesized that it might be involved in the pathophysiology of atherosclerotic diseases, which are regarded as chronic inflammatory diseases. Serum PGLYRP1 concentrations were measured in 240 patients with coronary artery disease (CAD) and 209 age-matched and gender-matched individuals with normal coronary arteries using enzyme-linked immunosorbent assay. The expression of PGLYRP1 in atherosclerotic plaques was quantified using western blotting and immunostaining. ApoE-/- mice, fed a high-fat diet, were randomly given intraperitoneal injections of saline or recombinant PGLYRP1 protein for 12 weeks. The effects of PGLYRP1 on human umbilical vein endothelial cells were investigated by western blotting. Higher concentrations of PGLYRP1 were significantly associated with a higher risk of CAD. The odd ratio for upper quartile versus lower quartile was 2.24 (95% confidence interval: 1.21-4.13) after adjustment for sex, age, smoking, body mass index, lipid profile, blood pressure, fasting glucose, and estimated glomerular filtration rate. PGLYRP1 was highly expressed in murine atherosclerotic plaques. Recombinant PGLYRP1 protein alleviated the progress of atherosclerosis in vivo and reduced the expression of endothelial cells' adhesion molecules in vitro. In conclusion, our study suggested that PGLYRP1 is upregulated in patients with CAD and atherosclerotic plaques. PGLYRP1 may participate in the pathophysiological process of atherosclerosis.

摘要

肽聚糖识别蛋白 1(PGLYRP1)长期以来被认为在感染和免疫性疾病中发挥重要作用。我们假设它可能与动脉粥样硬化性疾病的病理生理学有关,因为动脉粥样硬化性疾病被认为是慢性炎症性疾病。采用酶联免疫吸附试验检测 240 例冠心病(CAD)患者和 209 例年龄和性别匹配的正常冠状动脉患者的血清 PGLYRP1 浓度。采用 Western blot 和免疫染色定量检测动脉粥样硬化斑块中 PGLYRP1 的表达。采用高脂肪饮食喂养 ApoE-/- 小鼠,随机给予腹腔注射生理盐水或重组 PGLYRP1 蛋白 12 周。采用 Western blot 研究 PGLYRP1 对人脐静脉内皮细胞的影响。

与 CAD 风险升高显著相关的是 PGLYRP1 浓度较高。在校正性别、年龄、吸烟、体重指数、血脂、血压、空腹血糖和估算肾小球滤过率后,上四分位数与下四分位数的比值为 2.24(95%置信区间:1.21-4.13)。PGLYRP1 在鼠动脉粥样硬化斑块中高表达。重组 PGLYRP1 蛋白可减轻体内动脉粥样硬化的进展,并降低体外内皮细胞黏附分子的表达。

综上所述,本研究提示 CAD 患者和动脉粥样硬化斑块中 PGLYRP1 表达上调。PGLYRP1 可能参与动脉粥样硬化的病理生理过程。

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