动脉粥样硬化关键作用

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引用次数: 1

摘要

心血管疾病(cvd)仍然是全世界死亡和过早死亡的主要原因。在印度尼西亚,心血管疾病占非传染性疾病主要死亡原因的35%,其次是糖尿病,占6%。缺血性心脏病和急性缺血性中风是印尼动脉粥样硬化导致死亡的主要原因。动脉粥样硬化是一个多因素的病因,慢性炎症可引起心肌梗死和急性缺血性中风。研究表明,动脉粥样硬化的潜在机制之一是炎症。目前的研究表明,炎症可以激活细胞质蛋白复合物,即核苷酸结合寡聚化结构域样受体家族pyrin结构域3 (NLRP3)炎性体。NLRP3炎症小体是一种蛋白质传感器,对危险信号做出反应,称为病原体相关分子模式(PAMPs)或损伤/危险相关分子模式(DAMPs)。NLRP3炎性小体将前il -1 β和前il -18转化为成熟形式,通过裂解Caspase-1引发细胞死亡(焦亡)。这种NLRP3炎症小体通过影响其细胞和分子靶点的序列,在动脉粥样硬化的发生和进展中起核心作用。迄今为止,一些小分子和药物已被确定为NLRP3炎症小体抑制途径和动脉粥样硬化的潜在治疗剂。在这篇综述中,我们将进一步讨论NLRP3炎症小体的结构及其在动脉粥样硬化中的作用,以及炎症小体途径中靶向的小分子和药物的潜在候选者。
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Peran Penting Inflamasom NLRP3 pada Aterosklerosis
Cardiovascular diseases (CVDs) still contribute as the main cause of mortality and premature mortality worldwide. In Indonesia, CVDs contribute to 35% of the main cause of death in non-communicable diseases followed by diabetes at 6%. The ischemic heart disease and acute ischemic stroke is the main cause of death in Indonesia due to atherosclerosis. Atherosclerosis is a multifactorial cause, with chronic inflammation which causes myocardial infarction and acute ischemic stroke. Research demonstrated that one of the underlying mechanisms of atherosclerosis is inflammation. The current research suggested that inflammation could activate a complex of cytosol proteins, namely nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome. The NLRP3 inflammasome is known as a protein sensor as a response to danger signals known as pathogen-associated molecular patterns (PAMPs) or damage/danger-associated molecular patterns (DAMPs). The NLRP3 inflammasome will convert the pro-IL1β and pro-IL-18 into their mature forms which initiates the cell death (pyroptosis) through the cleavage of Caspase-1. This NLRP3 inflammasome has a central role in the initiation and progression of atherosclerosis by affecting the sequences of its cellular and molecular targets. To date, several small molecules and drugs have been identified as NLRP3 inflammasome inhibitory pathways and potential therapeutic agents for atherosclerosis. In this review, we will discuss further the structure of NLRP3 inflammasome and its roles in atherosclerosis, and the potential candidates of the small molecules and drugs targeted in the inflammasome pathway.
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