Center for Excellence in Vascular Biology, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA.
Center for Excellence in Vascular Biology, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA; Center for Interdisciplinary Cardiovascular Sciences, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA; Department of Pathology, Sechenov First Moscow State Medical University, Moscow, 119992, Russia.
Atherosclerosis. 2020 Aug;306:59-67. doi: 10.1016/j.atherosclerosis.2020.02.016. Epub 2020 Feb 28.
Despite the focus placed on cardiovascular research, the prevalence of vascular and valvular calcification is increasing and remains a leading contributor of cardiovascular morbidity and mortality. Accumulating studies provide evidence that cardiovascular calcification is an inflammatory disease in which innate immune signaling becomes sustained and/or excessive, shaping a deleterious adaptive response. The triggering immune factors and subsequent inflammatory events surrounding cardiovascular calcification remain poorly understood, despite sustained significant research interest and support in the field. Most studies on cardiovascular calcification focus on innate cells, particularly macrophages' ability to release pro-osteogenic cytokines and calcification-prone extracellular vesicles and apoptotic bodies. Even though substantial evidence demonstrates that macrophages are key components in triggering cardiovascular calcification, the crosstalk between innate and adaptive immune cell components has not been adequately addressed. The only therapeutic options currently used are invasive procedures by surgery or transcatheter intervention. However, no approved drug has shown prophylactic or therapeutic effectiveness. Conventional diagnostic imaging is currently the best method for detecting, measuring, and assisting in the treatment of calcification. However, these common imaging modalities are unable to detect early subclinical stages of disease at the level of microcalcifications; therefore, the vast majority of patients are diagnosed when macrocalcifications are already established. In this review, we unravel the current knowledge of how innate and adaptive immunity regulate cardiovascular calcification; and put forward differences and similarities between vascular and valvular disease. Additionally, we highlight potential immunomodulatory drugs with the potential to target calcification and propose avenues in need of further translational inquiry.
尽管心血管研究受到关注，但血管和瓣膜钙化的患病率正在增加，仍然是心血管发病率和死亡率的主要原因。越来越多的研究证据表明，心血管钙化是一种炎症性疾病，其中先天免疫信号持续存在和/或过度，形成有害的适应性反应。尽管该领域持续有大量的研究兴趣和支持，但心血管钙化周围的触发免疫因素和随后的炎症事件仍知之甚少。大多数心血管钙化的研究都集中在先天细胞上，特别是巨噬细胞释放促成骨细胞细胞因子和易钙化的细胞外囊泡和凋亡小体的能力。尽管大量证据表明巨噬细胞是触发心血管钙化的关键组成部分，但先天免疫细胞和适应性免疫细胞成分之间的相互作用尚未得到充分解决。目前使用的唯一治疗选择是手术或经导管介入的侵入性程序。然而，没有一种批准的药物显示出预防或治疗效果。传统的诊断成像目前是检测、测量和辅助钙化治疗的最佳方法。然而，这些常见的成像方式无法在微钙化水平检测到疾病的早期亚临床阶段；因此，绝大多数患者在已经存在大钙化时才被诊断出来。在这篇综述中，我们揭示了先天免疫和适应性免疫如何调节心血管钙化的现有知识；并提出了血管和瓣膜疾病之间的差异和相似之处。此外，我们强调了具有靶向钙化潜力的潜在免疫调节药物，并提出了需要进一步转化研究的途径。
