National Medical Research Center of Cardiology named after academician E.I. Chazov, Moscow, Russia.
National Medical Research Center of Cardiology named after academician E.I. Chazov, Moscow, Russia.
Cardiovasc Pathol. 2022 Sep-Oct;60:107452. doi: 10.1016/j.carpath.2022.107452. Epub 2022 Jul 16.
Coxsackie Virus and Adenovirus Receptor (CXADR or CAR) is involved in the pathogenesis of inflammatory dilated cardiomyopathy (DCM). We aimed to examine the relationship of CAR expression on platelets and cardiomyocytes with virus persistence, local and systemic inflammation and platelet activity in patients with DCM.
Endomyocardial biopsy (EMB) samples of 38 patients (mean age 39.5±11.3 years, 20 male) with DCM were analyzed for CAR expression, local inflammation grade by immunohistochemistry and virus persistence by real-time PCR. Platelet morphology was analyzed in all patients and 30 healthy subjects (HS) using scanning electron microscopy, platelet activity by light transmission aggregation, and CAR persistence by immunofluorescence. Platelets of 20 patients were analyzed for cytomegalovirus and herpes simplex virus 1-2 by immunofluorescence. Serum levels of tumor necrosis factor alpha (TNF α) and Interleukin-6 were assessed using ELISA in all studied subjects.
CAR expression in EMB samples was related to the heart failure functional class and the level of IL-6. Platelets from DCM patients showed enhanced spontaneous and ADP induced aggregation. Platelets' CAR expression was >4 fold higher in DCM than HS and was observed predominantly at sites of intercellular communications in microaggregates and leukocyte-platelet aggregates. CAR-positive patients showed significantly higher TNF-α and IL-6 serum levels in CAR-negative patients. Platelets of 6 (30%) DCM patients revealed the mature cytomegalovirus and herpes simplex viruses particles.
Tight junction protein CAR may serve as a docking pin creating a new type of contact structure that could be responsible for signaling between neighboring cells in pathological conditions.
柯萨奇病毒和腺病毒受体（CXADR 或 CAR）参与了炎症性扩张型心肌病（DCM）的发病机制。我们旨在研究 CAR 在血小板和心肌细胞中的表达与病毒持续存在、局部和全身炎症以及 DCM 患者血小板活性之间的关系。
对 38 例 DCM 患者（平均年龄 39.5±11.3 岁，20 名男性）的心肌内膜活检（EMB）样本进行 CAR 表达、免疫组织化学检测局部炎症程度和实时 PCR 检测病毒持续存在的分析。对所有患者和 30 名健康对照者（HS）进行血小板形态学分析，采用扫描电子显微镜；血小板活性分析，采用透光比浊法；CAR 持续存在分析，采用免疫荧光法。对 20 例患者的血小板进行巨细胞病毒和单纯疱疹病毒 1-2 的免疫荧光分析。采用 ELISA 法检测所有研究对象的血清肿瘤坏死因子-α（TNFα）和白细胞介素-6（IL-6）水平。
EMB 样本中的 CAR 表达与心力衰竭功能分级和 IL-6 水平有关。DCM 患者的血小板自发性和 ADP 诱导性聚集增强。DCM 患者的血小板 CAR 表达比 HS 高>4 倍，主要在微聚集物和白细胞-血小板聚集物的细胞间通讯部位观察到。CAR 阳性患者的 TNF-α和 IL-6 血清水平明显高于 CAR 阴性患者。6 例（30%）DCM 患者的血小板显示出成熟的巨细胞病毒和单纯疱疹病毒颗粒。
紧密连接蛋白 CAR 可作为一种对接销，形成一种新的接触结构，这种结构可能负责在病理条件下相邻细胞之间的信号传递。
