Nasuno Akimitsu, Toba Ken, Ozawa Takuya, Hanawa Haruo, Osman Yasser, Hotta Yuko, Yoshida Kaori, Saigawa Takashi, Kato Kiminori, Kuwano Ryozo, Watanabe Kenichi, Aizawa Yoshifusa
Division of Cardiology, Niigata University Graduate School of Medical and Dental Sciences, l-754 Asahimachi-dori, Niigata 951-8510, Japan.
Cardiovasc Pathol. 2004 Mar-Apr;13(2):79-84. doi: 10.1016/S1054-8807(03)00137-6.
Our previous study revealed that the coxsackievirus and adenovirus receptor (CAR) is a homophilic cell adhesion molecule and may function as a sensor of cell-cell interactions in the brain and damaged heart. In this study, we investigated if CAR expression is involved in the formation of neointimal hyperplasia using a balloon injury model of rat carotid artery. Cultured vascular smooth muscle cells (SMCs) from rat aorta were also studied. CAR antigen was constitutively detected in the endothelial cells (ECs) but not in SMCs before injury. On Day 5 after balloon injury, CAR was expressed strongly in the first layer of medial SMCs. Neointimal hyperplasia was observed on Day 7, and strong expressions of CAR concomitantly with proliferating cell nuclear antigen (PCNA) were obvious in the neointimal SMCs, while CAR in medial SMCs disappeared. The expression of CAR mRNA reached a peak on Day 7 and declined gradually to the basal levels. When the ECs regenerated on Day 14, CAR antigen was observed in the ECs but disappeared in the neointima. CAR together with PCNA was expressed abundantly in the proliferating SMCs in vitro and diminished in cells grown to a confluent state. The abundant expression of CAR in the neointima may facilitate an adenoviral gene therapy.
我们之前的研究表明，柯萨奇病毒和腺病毒受体（CAR）是一种同源性细胞黏附分子，可能在大脑和受损心脏中作为细胞间相互作用的传感器。在本研究中，我们使用大鼠颈动脉球囊损伤模型研究了CAR表达是否参与新生内膜增生的形成。还对来自大鼠主动脉的培养血管平滑肌细胞（SMC）进行了研究。在损伤前，CAR抗原在内皮细胞（EC）中可组成性检测到，但在SMC中未检测到。球囊损伤后第5天，CAR在内侧SMC的第一层中强烈表达。在第7天观察到新生内膜增生，新生内膜SMC中CAR与增殖细胞核抗原（PCNA）的强表达明显，而内侧SMC中的CAR消失。CAR mRNA的表达在第7天达到峰值，然后逐渐下降至基础水平。当EC在第14天再生时，在EC中观察到CAR抗原，但在新生内膜中消失。在体外，CAR与PCNA在增殖的SMC中大量表达，而在生长至汇合状态的细胞中减少。新生内膜中CAR的大量表达可能有助于腺病毒基因治疗。
