動(dòng)脈粥樣硬化（atheroma)是一組動(dòng)脈硬化的血管病中常見的最重要的一種,，其特點(diǎn)是受累動(dòng)脈病變從內(nèi)膜開始,。一般先有脂質(zhì)和復(fù)合糖類積聚、出血及血栓形成,，纖維組織增生及鈣質(zhì)沉著,，并有動(dòng)脈中層的逐漸蛻變和鈣化，病變常累及彈性及大中等肌性動(dòng)脈,，一旦發(fā)展到足以阻塞動(dòng)脈腔,，則該動(dòng)脈所供應(yīng)的組織或器官將缺血或壞死。由于在動(dòng)脈內(nèi)膜積聚的脂質(zhì)外觀呈黃色粥樣,，因此稱為動(dòng)脈粥樣硬化,。
對(duì)吃高膽固醇食物、易患動(dòng)脈粥樣硬化癥的（缺少“載脂蛋白E”的）小鼠所做一項(xiàng)研究表明,，小膽固醇晶體會(huì)出現(xiàn)在動(dòng)脈粥樣硬化的最早階段,，而且這些晶體能激發(fā)吞噬細(xì)胞中的NLRP3炎性體。
這表明,，減少膽固醇沉積或阻斷炎性體通道的治療策略可能具有抗動(dòng)脈粥樣硬化效果,。(生物谷Bioon.com)
生物谷推薦原文出處：
Nature doi:10.1038/nature08938
NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals
Peter Duewell,Hajime Kono,Katey J. Rayner,Cherilyn M. Sirois,Gregory Vladimer,Franz G. Bauernfeind,George S. Abela,Luigi Franchi,Gabriel Nu?ez,Max Schnurr,Terje Espevik,Egil Lien,Katherine A. Fitzgerald,Kenneth L. Rock,Kathryn J. Moore,Samuel D. Wright,Veit Hornung& Eicke Latz
The inflammatory nature of atherosclerosis is well established but the agent(s) that incite inflammation in the artery wall remain largely unknown. Germ-free animals are susceptible to atherosclerosis, suggesting that endogenous substances initiate the inflammation1. Mature atherosclerotic lesions contain macroscopic deposits of cholesterol crystals in the necrotic core, but their appearance late in atherogenesis had been thought to disqualify them as primary inflammatory stimuli. However, using a new microscopic technique, we revealed that minute cholesterol crystals are present in early diet-induced atherosclerotic lesions and that their appearance in mice coincides with the first appearance of inflammatory cells. Other crystalline substances can induce inflammation by stimulating the caspase-1-activating NLRP3 (NALP3 or cryopyrin) inflammasome2, 3, which results in cleavage and secretion of interleukin (IL)-1 family cytokines. Here we show that cholesterol crystals activate the NLRP3 inflammasome in phagocytes in vitro in a process that involves phagolysosomal damage. Similarly, when injected intraperitoneally, cholesterol crystals induce acute inflammation, which is impaired in mice deficient in components of the NLRP3 inflammasome, cathepsin B, cathepsin L or IL-1 molecules. Moreover, when mice deficient in low-density lipoprotein receptor (LDLR) were bone-marrow transplanted with NLRP3-deficient, ASC (also known as PYCARD)-deficient or IL-1α/β-deficient bone marrow and fed on a high-cholesterol diet, they had markedly decreased early atherosclerosis and inflammasome-dependent IL-18 levels. Minimally modified LDL can lead to cholesterol crystallization concomitant with NLRP3 inflammasome priming and activation in macrophages. Although there is the possibility that oxidized LDL activates the NLRP3 inflammasome in vivo, our results demonstrate that crystalline cholesterol acts as an endogenous danger signal and its deposition in arteries or elsewhere is an early cause rather than a late consequence of inflammation. These findings provide new insights into the pathogenesis of atherosclerosis and indicate new potential molecular targets for the therapy of this disease.
