Social Determinants of Obesity and Cardiovascular Risk Laboratory, National Heart, Lung, and Blood Institute, Building 10, 10 Center Drive, Bethesda, MD, 20814, USA.
Dept. of Medicine, University of California San Diego, 9500 Gilman Street, La Jolla, CA, 92093, USA.
Adv Biol (Weinh). 2021 Nov;5(11):e2100638. doi: 10.1002/adbi.202100638. Epub 2021 Sep 29.
Cholesterol crystals (CCs) were first discovered in atherosclerotic plaque tissue in the early 1900 and have since been observed and implicated in many diseases and conditions, including myocardial infarction, abdominal aortic aneurism, kidney disease, ocular diseases, and even central nervous system anomalies. Despite the widespread involvement of CCs in many pathologies, the mechanisms involved in their formation and their role in various diseases are still not fully understood. Current knowledge concerning the formation of CCs, as well as the molecular pathways activated upon cellular exposure to CCs, will be explored in this review. As CC formation is tightly associated with lipid metabolism, the role of cellular lipid homeostasis in the formation of CCs is highlighted, including the role of lysosomes. In addition, cellular pathways and processes known to be affected by CCs are described. In particular, CC-induced activation of the inflammasome and production of reactive oxygen species, along with the role of CCs in complement-mediated inflammation is discussed. Moreover, the clinical manifestation of embolized CCs is described with a focus on renal and skin diseases associated with CC embolism. Lastly, potential therapeutic measures that target either the formation of CCs or their impact on different cell types and tissues are highlighted.
胆固醇晶体（CCs）于 20 世纪初首次在动脉粥样硬化斑块组织中被发现，此后在许多疾病和病症中均有观察到 CCs 的存在并认为其与这些疾病相关，包括心肌梗死、腹主动脉瘤、肾脏疾病、眼部疾病，甚至中枢神经系统异常。尽管 CCs 广泛参与了许多病理学过程，但它们的形成机制及其在各种疾病中的作用仍未完全阐明。本综述将探讨 CC 形成的相关知识，以及细胞暴露于 CCs 后激活的分子途径。由于 CC 的形成与脂质代谢密切相关，因此强调了细胞脂质稳态在 CC 形成中的作用，包括溶酶体的作用。此外，还描述了已知受 CC 影响的细胞途径和过程。特别地，讨论了 CC 诱导的炎症小体激活和活性氧的产生，以及 CC 在补体介导的炎症中的作用。此外，还描述了栓塞的 CC 引发的临床表现，重点是与 CC 栓塞相关的肾脏和皮肤疾病。最后，强调了针对 CC 形成或其对不同细胞类型和组织的影响的潜在治疗措施。
