Mathieu Patrick, Bouchareb Rihab, Boulanger Marie-Chloé
Laboratoire d'Études Moléculaires des Valvulopathies (LEMV), Groupe de Recherche en Valvulopathies (GRV), Quebec Heart and Lung Institute/Research Center, Department of Surgery, Laval University, QC, Canada ; Institut de Cardiologie et de Pneumologie de Québec, 2725 Chemin Sainte-Foy, Québec, QC, Canada G1V 4G5.
J Immunol Res. 2015;2015:851945. doi: 10.1155/2015/851945. Epub 2015 May 3.
Calcific aortic valve disease (CAVD) is the most common heart valve disorder. CAVD is a chronic process characterized by a pathologic mineralization of valve leaflets. Ectopic mineralization of the aortic valve involves complex relationships with immunity. Studies have highlighted that both innate and adaptive immunity play a role in the development of CAVD. In this regard, accumulating evidence indicates that fibrocalcific remodelling of the aortic valve is associated with activation of the NF-κB pathway. The expression of TNF-α and IL-6 is increased in human mineralized aortic valves and promotes an osteogenic program as well as the mineralization of valve interstitial cells (VICs), the main cellular component of the aortic valve. Different factors, including oxidized lipid species, activate the innate immune response through the Toll-like receptors. Moreover, VICs express 5-lipoxygenase and therefore produce leukotrienes, which may amplify the inflammatory response in the aortic valve. More recently, studies have emphasized that an adaptive immune response is triggered during CAVD. Herein, we are reviewing the link between the immune response and the development of CAVD and we have tried, whenever possible, to keep a translational approach.
钙化性主动脉瓣疾病（CAVD）是最常见的心脏瓣膜疾病。CAVD是一个慢性过程，其特征是瓣膜小叶发生病理性矿化。主动脉瓣的异位矿化涉及与免疫的复杂关系。研究强调，先天性免疫和适应性免疫在CAVD的发展中均起作用。在这方面，越来越多的证据表明，主动脉瓣的纤维钙化重塑与NF-κB信号通路的激活有关。在人类矿化主动脉瓣中，TNF-α和IL-6的表达增加，并促进成骨程序以及瓣膜间质细胞（VICs）的矿化，VICs是主动脉瓣的主要细胞成分。包括氧化脂质在内的不同因素通过Toll样受体激活先天性免疫反应。此外，VICs表达5-脂氧合酶，因此产生白三烯，这可能会放大主动脉瓣中的炎症反应。最近，研究强调在CAVD过程中会触发适应性免疫反应。在此，我们综述免疫反应与CAVD发展之间的联系，并尽可能采用转化医学的方法。
