Folmsbee Stephen Sai, Gottardi Cara J
Departments of 1 Pulmonary and Critical Care Medicine.
2 The Driskill Graduate Training Program in Life Sciences, and.
Am J Respir Cell Mol Biol. 2017 Nov;57(5):512-518. doi: 10.1165/rcmb.2016-0261TR.
Recent genome-wide association studies have implicated both cardiac and pulmonary vein-related genes in the pathogenesis of asthma. Since cardiac cells are not present in lung airways or viewed to affect the immune system, interpretation of these findings in the context of more well-established contributors to asthma has remained challenging. However, cardiomyocytes are present in the lung, specifically along pulmonary veins, and recent murine models suggest that cardiac cells lining the pulmonary veins may contribute to allergic airway disease. Notably, the cardiac cell-junction protein αT-catenin (αT-cat, CTNNA3), which is implicated in occupational and steroid-resistant asthma by clinical genetic data, appears to play an important role in regulating inflammation around the cardiac cells of pulmonary veins. Beyond the potential contribution of pulmonary veins, clinical data directly examining cardiac function through echocardiography have found strong associations between asthmatic phenotypes and the mechanical properties of the heart. Together, these data suggest that targeting the function of cardiac cells in the pulmonary veins and/or heart may allow for novel and potentially efficacious therapies for asthma, particularly in challenging cases of steroid-resistant asthma.
最近的全基因组关联研究表明,心脏和肺静脉相关基因均与哮喘的发病机制有关。由于肺气道中不存在心脏细胞,也不认为其会影响免疫系统,因此在哮喘的其他公认病因背景下解释这些发现仍然具有挑战性。然而,心肌细胞存在于肺中,特别是沿着肺静脉分布,最近的小鼠模型表明,肺静脉内衬的心脏细胞可能与过敏性气道疾病有关。值得注意的是,临床遗传数据表明与职业性和类固醇抵抗性哮喘相关的心脏细胞连接蛋白αT-连环蛋白(αT-cat,CTNNA3),似乎在调节肺静脉心脏细胞周围的炎症中起重要作用。除了肺静脉的潜在作用外,通过超声心动图直接检查心脏功能的临床数据发现,哮喘表型与心脏的机械特性之间存在密切关联。总之,这些数据表明,针对肺静脉和/或心脏中心脏细胞的功能进行治疗,可能为哮喘提供新的、潜在有效的治疗方法,特别是在类固醇抵抗性哮喘的疑难病例中。