Hashimoto Hirotsugu, Kurata Atsushi, Nashiro Tamaki, Inoue Shigeru, Ushijima Tomonori, Fujita Koji, Kimura Toshikazu, Kawai Kensuke, Horiuchi Hajime, Kuroda Masahiko
Department of Molecular Pathology, Tokyo Medical UniversityTokyo, Japan; Department of Diagnostic Pathology, NTT Medical Center TokyoTokyo, Japan.
Department of Molecular Pathology, Tokyo Medical University Tokyo, Japan.
Int J Clin Exp Pathol. 2015 Nov 1;8(11):14630-9. eCollection 2015.
Although immaturity of neointimal smooth muscle cells (SMCs) in coronary arteries has recently been demonstrated to be associated with acute coronary syndrome, the carotid arterial counterpart has not been investigated. We hypothesized that the same investigation of carotid endarterectomy specimens might contribute to living patients. Carotid endarterectomy specimens from 33 Asian males who underwent a 5-year follow-up were examined. Age, atherosclerotic risk factors, and percentage stenosis were investigated. Histologically, the fibrous cap/lipid core ratio was measured. Maturation of SMCs was assessed by the h-caldesmon/smooth muscle actin (SMA) ratio by immunohistochemistry in 3 different regions (luminal, medial, and opposite side of lipid core) in the neointima. Associations of these factors with preoperative symptoms along with postoperative systemic atherogenic cardiovascular events were analyzed. It was revealed that fibrous cap/lipid core ratio was significantly lower in symptomatic than in asymptomatic patients, while the h-caldesmon/SMA ratio was significantly lower in patients with than without postoperative systemic atherogenic cardiovascular events by the Student's t-test (P<0.05). Logistic regression model demonstrated that younger age and a lower h-caldesmon/SMA ratio were associated with postoperative systemic atherogenic cardiovascular events (P<0.05). This result was not different when 3 different regions were each analyzed instead. Immaturity of neointimal SMCs shown by a lower h-caldesmon/SMA ratio by immunohistochemistry was associated with systemic atherogenic cardiovascular events. Thus, this finding may be predictive of these events after carotid endarterectomy. Uniform results among different neointimal regions suggest that immaturity of neointimal SMCs causes plaque instability and does not occur secondarily to plaque instability.
尽管最近已证明冠状动脉中新内膜平滑肌细胞（SMC）的不成熟与急性冠状动脉综合征有关，但尚未对颈动脉中的情况进行研究。我们假设，对颈动脉内膜切除术标本进行同样的研究可能有助于现存患者。对33名接受了5年随访的亚洲男性的颈动脉内膜切除术标本进行了检查。调查了年龄、动脉粥样硬化危险因素和狭窄百分比。组织学上，测量了纤维帽/脂质核心比率。通过免疫组织化学在新内膜的3个不同区域（管腔、中膜和脂质核心的对侧）中通过h-钙调蛋白/平滑肌肌动蛋白（SMA）比率评估SMC的成熟度。分析了这些因素与术前症状以及术后全身性动脉粥样硬化性心血管事件之间的关联。结果显示，有症状患者的纤维帽/脂质核心比率显著低于无症状患者，而通过学生t检验，有术后全身性动脉粥样硬化性心血管事件的患者的h-钙调蛋白/SMA比率显著低于无此类事件的患者（P<0.05）。逻辑回归模型表明，年龄较小和h-钙调蛋白/SMA比率较低与术后全身性动脉粥样硬化性心血管事件相关（P<0.05）。对3个不同区域分别进行分析时，结果并无差异。免疫组织化学显示的新内膜SMC不成熟，以较低的h-钙调蛋白/SMA比率为特征，与全身性动脉粥样硬化性心血管事件相关。因此，这一发现可能有助于预测颈动脉内膜切除术后的这些事件。不同新内膜区域的一致结果表明，新内膜SMC的不成熟会导致斑块不稳定，而非继发于斑块不稳定。
