Formation and Cellular Impact of Cholesterol Crystals in Health and Disease.
Formation and Cellular Impact of Cholesterol Crystals in Health and Disease.
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DOI：
10.1002/adbi.202100638
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发表时间：
2021-09
期刊：
影响因子：
3.7
通讯作者：
Y. Baumer;Sara McCurdy;W. Boisvert
中科院分区：
文献类型：
--
作者：
Y. Baumer;Sara McCurdy;W. Boisvert
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，此后被观察到并与许多疾病和病症有关，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cc广泛参与许多病理，但其形成的机制及其在各种疾病中的作用仍未完全了解。本综述将探讨目前有关CCs形成的知识，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CCs影响的细胞途径和过程。特别是，cc诱导炎症小体的激活和活性氧的产生，以及cc在补体介导的炎症中的作用被讨论。此外，CC栓塞的临床表现主要描述了与CC栓塞相关的肾脏和皮肤疾病。最后，强调了针对CCs形成或其对不同细胞类型和组织的影响的潜在治疗措施。
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.