Department of General Surgery, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, 2800 Gongwei Road, Pudong, Shanghai 201399, China.
Department of General Surgery, Huashan Hospital, Fudan University, Shanghai, China.
Cardiovasc Pathol. 2020 Nov-Dec;49:107258. doi: 10.1016/j.carpath.2020.107258. Epub 2020 Jun 24.
Advanced atherosclerotic plaques tend to indicate an increased risk of cerebral ischemic events. SH2 domain-containing protein tyrosine phosphatase 1 (SHP-1) is a class I classical nonreceptor protein tyrosine phosphatase associated with plaque stability, as shown by analysis of a Gene Expression Omnibus (GEO) dataset showing differences in mRNA levels. However, the correlation between SHP-1 and human carotid plaque stability at the protein level remains unclear.
Thirty-nine carotid plaque tissue samples were acquired from 39 carotid artery stenosis patients after carotid endarterectomy. Hematoxylin and eosin, Masson trichrome, and CD68 staining was performed for pathological characterization, and immunohistochemical staining for SHP-1 was carried out. Within stable and unstable plaques, SHP-1 mainly accumulated in the necrotic area, plaque shoulder, and fibrous cap, similar to the distribution of CD68. A quantitative analysis of SHP-1 was carried out. The relative SHP-1-positive cell area was higher in the vulnerable group than in the stable group (P < .001). The number of symptomatic patients in the vulnerable group was no greater than that in the stable group (P = .098). Moreover, the integrated optical density (IOD)/area of SHP-1 was significantly higher in the vulnerable group than in the stable group (P < .001). Besides, SHP-1 colocalized with CD68 and vascular cell adhesion protein 1(VCAM-1).
We demonstrate that SHP-1 expression increases during carotid atherosclerotic plaque progression. The protein expression of SHP-1 was related to an increase in plaque instability in not only symptomatic but also asymptomatic patients with carotid artery stenosis. SHP-1 may play a role in atherosclerosis progression by macrophage polarization-mediated efferocytosis. Furthermore, SHP-1 may become a promising biomarker for plaque vulnerability in the future.
进展性动脉粥样硬化斑块往往提示发生脑缺血事件的风险增加。SH2 域结合蛋白酪氨酸磷酸酶 1（SHP-1）是与斑块稳定性相关的 I 类经典非受体蛋白酪氨酸磷酸酶，这可通过基因表达综合数据库（GEO）数据集分析显示 mRNA 水平差异得到证实。然而，在蛋白质水平上 SHP-1 与人类颈动脉斑块稳定性之间的相关性尚不清楚。
39 例颈动脉内膜切除术患者的 39 个颈动脉斑块组织样本。进行苏木精和伊红、马松三色和 CD68 染色进行病理特征分析，并进行 SHP-1 免疫组织化学染色。在稳定和不稳定斑块内，SHP-1 主要在坏死区、斑块肩部和纤维帽中积聚，与 CD68 的分布相似。对 SHP-1 进行定量分析。易损组的 SHP-1 阳性细胞面积比稳定组高（P<0.001）。易损组有症状患者的数量不比稳定组多（P=0.098）。此外，易损组的 SHP-1 积分光密度（IOD）/面积明显高于稳定组（P<0.001）。此外，SHP-1 与 CD68 和血管细胞黏附蛋白 1（VCAM-1）共定位。
我们证明 SHP-1 在颈动脉粥样硬化斑块进展过程中表达增加。SHP-1 的蛋白表达不仅与有症状患者颈动脉狭窄斑块不稳定增加有关，也与无症状患者斑块不稳定增加有关。SHP-1 可能通过巨噬细胞极化介导的噬斑作用在动脉粥样硬化进展中发挥作用。此外，SHP-1 可能成为未来斑块易损性的有前途的生物标志物。
