A Decline in Platelet Activation and Inflammatory Cell Infiltration is Associated with the Phenotypic Redifferentiation of Neointimal Smooth Muscle Cells after Bare-metal Stent Implantation in Acute Coronary Syndrome
A Decline in Platelet Activation and Inflammatory Cell Infiltration is Associated with the Phenotypic Redifferentiation of Neointimal Smooth Muscle Cells after Bare-metal Stent Implantation in Acute Coronary Syndrome
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DOI：
10.5551/jat.3426
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发表时间：
2010-01-01
影响因子：
4.4
通讯作者：
Ueda, Makiko
中科院分区：
文献类型：
--
作者：
Nakagawa, Masashi;Naruko, Takahiko;Ueda, Makiko
目的：免疫组化检测急性冠状动脉综合征（ACS）患者裸金属支架（BMS）部位血小板活化/聚集、炎症细胞浸润、新生内膜平滑肌细胞（SMC）分化状态、血小板衍生生长因子（PDGF）表达与内皮细胞再生的关系。从ACS患者尸检中获得16支支架植入后的冠状动脉。用抗SMC（1A 4、HHF-35、CGA-7）、巨噬细胞、中性粒细胞、内皮细胞、GP IIb/IIIa、P-selectin、PDGF-B和PDGF-beta receptor.Results的抗体对连续冰冻切片进行染色。BMS术后24 ~ 55 d，部分血小板血栓仍呈P-选择素阳性，同时可见中性粒细胞和巨噬细胞浸润，新生内膜平滑肌细胞1A 4染色阳性，CGA-7染色阴性，巨噬细胞和平滑肌细胞表达PDGF-B和PDGF-beta受体。在3个月后的部位，未检测到血小板血栓和中性粒细胞浸润，新生内膜中CGA-7阳性的高分化SMC数量增加。P-选择素阳性面积与中性粒细胞计数和巨噬细胞阳性面积正相关（中性粒细胞，r = 0.86，p < 0.0005;巨噬细胞，r = 0.66，p < 0.05）。而P-选择素阳性面积与HHF-35阳性面积和CGA-7阳性面积呈负相关（HHF-35，r =-0.90，p < 0.0001; CGA-7，r =-0.82，p < 0.005）。这些观察结果表明，P-选择素-ACS患者BMS术后新生内膜中血小板血栓阳性与炎性细胞浸润呈正相关，而炎症反应与新生内膜SMC表型再分化呈正相关。
Aim: This immunohistochemical investigation was to analyze the relationship between platelet activation/aggregation, inflammatory cell infiltration, the differentiation state of neointimal smooth muscle cells (SMCs), expression of platelet-derived growth factor (PDGF), and endothelial cell regeneration at sites of bare-metal stents (BMS) in patients with acute coronary syndrome (ACS).Methods: Sixteen coronary arteries after stenting were obtained at autopsy from ACS patients. Serial frozen sections were stained with antibodies against SMCs (1A4, HHF-35, CGA-7), macrophages, neutrophils, endothelial cells, GP IIb/IIIa, P-selectin, PDGF-B, and PDGF-beta receptor.Results: Up to 12 days after BMS, the stent sites contained P-selectin-positive activated platelets with neutrophil infiltration. From 24 to 55 days after BMS, parts of the platelet thrombi were still positive for P-selectin, and infiltration of neutrophils and macrophages was also found. Neointimal SMCs at these stages stained positive with 1A4 but negative with CGA-7, and PDGF-B and PDGF-beta receptor were expressed in macrophages and SMCs. At sites from 3 months onward, platelet thrombi and neutrophil infiltration were not detected, and the neointima contained increased numbers of highly differentiated SMCs with CGA-7 positivity. The P-selectin-positive area was positively correlated with the neutrophil count and macrophage-positive area (neutrophils, r = 0.86, p < 0.0005; macrophage, r = 0.66, p < 0.05). In contrast, the P-selectin-positive area was negatively correlated with the HHF-35-positive area and CGA-7-positive area (HHF-35, r = -0.90, p < 0.0001; CGA-7, r = -0.82, p < 0.005).Conclusion: These observations suggest that P-selectin-positive platelet thrombi in the neointima are positively associated with the inflammatory cell infiltration and reversely associated with the phenotypic redifferentiation of neointimal SMCs after BMS in ACS patients.