Division of Cardiovascular Medicine, Department of Medicine, Center for Interdisciplinary Cardiovascular Sciences, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Division of Cardiovascular Medicine, Department of Medicine, Center for Excellence in Vascular Biology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Cardiovasc Res. 2021 Nov 22;117(13):2506-2524. doi: 10.1093/cvr/cvab273.
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.
钙化性主动脉瓣疾病（CAVD）及其临床表现——钙化性主动脉瓣狭窄，是发达国家瓣膜疾病的主要病因，目前尚无可用的药物治疗方法来延缓或阻止其进展。瓣膜疾病的特征是进行性纤维化重塑，随后瓣膜小叶发生病理性矿化，影响了 2.5%的西方人群，因此迫切需要进行干预。尽管瓣膜疾病的病理生物学机制复杂，涉及遗传因素、脂质浸润和氧化损伤，但免疫系统在发病机制和疾病持续发展中发挥关键作用的观点已被广泛接受。CAVD 不再被认为是一种被动退行性疾病，而是一种活跃的炎症过程，涉及多种促炎机制，适应性和固有免疫系统共同支撑着这些复杂机制。在瓣膜中，有 15%的细胞起源于造血系统，在炎症发生后，这一比例会大幅增加，因为巨噬细胞、T 淋巴细胞、B 淋巴细胞和固有免疫细胞会浸润瓣膜，促进进一步的炎症反应。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增，或者是两者的共同作用导致了疾病的进展，显然需要进一步了解免疫系统在瓣膜疾病中的作用，以便为控制 CAVD 发展提供未来的治疗策略。
