Calcific aortic valve disease (CAVD), and its clinical manifestation that is calcific aortic valve stenosis, is the leading cause for valve disease within the developed world, with no current pharmacological treatment available to delay or halt its progression. Characterized by progressive fibrotic remodelling and subsequent pathogenic mineralization of the valve leaflets, valve disease affects 2.5% of the western population, thus highlighting the need for urgent intervention. Whilst the pathobiology of valve disease is complex, involving genetic factors, lipid infiltration, and oxidative damage, the immune system is now being accepted to play a crucial role in pathogenesis and disease continuation. No longer considered a passive degenerative disease, CAVD is understood to be an active inflammatory process, involving a multitude of pro-inflammatory mechanisms, with both the adaptive and the innate immune system underpinning these complex mechanisms. Within the valve, 15% of cells evolve from haemopoietic origin, and this number greatly expands following inflammation, as macrophages, T lymphocytes, B lymphocytes, and innate immune cells infiltrate the valve, promoting further inflammation. Whether chronic immune infiltration or pathogenic clonal expansion of immune cells within the valve or a combination of the two is responsible for disease progression, it is clear that greater understanding of the immune systems role in valve disease is required to inform future treatment strategies for control of CAVD development.

中文翻译：

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先天性和适应性免疫：心脏瓣膜疾病的未充分研究的驱动力


钙化性主动脉瓣疾病（CAVD）及其钙化性主动脉瓣狭窄的临床表现是发达国家瓣膜疾病的主要原因，目前尚无药物治疗可延迟或阻止其进展。瓣膜疾病以瓣叶进行性纤维化重塑和随后的致病性矿化为特征，影响着 2.5% 的西方人口，因此迫切需要进行干预。虽然瓣膜疾病的病理学很复杂，涉及遗传因素、脂质浸润和氧化损伤，但现在人们普遍认为免疫系统在发病机制和疾病延续中发挥着至关重要的作用。 CAVD 不再被认为是一种被动退行性疾病，而是被认为是一种主动炎症过程，涉及多种促炎症机制，而适应性和先天免疫系统是这些复杂机制的基础。在瓣膜内，15% 的细胞从造血起源进化而来，并且随着巨噬细胞、T 淋巴细胞、B 淋巴细胞和先天免疫细胞浸润瓣膜，炎症后这一数字大大增加，从而促进进一步的炎症。无论是慢性免疫浸润还是瓣膜内免疫细胞的致病性克隆扩张，还是两者的组合都会导致疾病进展，很明显，需要更深入地了解免疫系统在瓣膜疾病中的作用，以便为未来控制瓣膜疾病的治疗策略提供信息。 CAVD 开发。