Shapiro Michael D, Fazio Sergio
Oregon Health & Science University, Knight Cardiovascular Institute, Center for Preventive Cardiology.
J Atheroscler Thromb. 2017 May 1;24(5):462-472. doi: 10.5551/jat.RV17003. Epub 2017 Mar 9.
Even though it is only a little over a decade from the discovery of proprotein convertase subtilisin/kexin type 9 (PCSK9) as a plasma protein that associates with both high and low cholesterol syndromes, a rich body of knowledge has developed, and drugs inhibiting this target have been approved in many markets. While the majority of research in recent years has focused on the impact of therapeutic antagonism of this molecule, important lines of investigation have emerged characterizing its unique physiology as it relates to cholesterol metabolism and atherosclerosis. The PCSK9 story is unfolding rapidly but is far from complete. One chapter that is of particular interest is the possible direct link between PCSK9 and atherosclerosis. This review specifically examines this relationship drawing from data produced from experimental models of plaque biology and inflammation, atherosclerosis imaging studies, and observational epidemiology.
尽管从发现前蛋白转化酶枯草溶菌素/kexin 9型（PCSK9）作为一种与高胆固醇和低胆固醇综合征均相关的血浆蛋白至今仅过去十多年，但已经积累了丰富的知识体系，并且抑制该靶点的药物已在许多市场获得批准。虽然近年来的大多数研究都集中在该分子治疗性拮抗作用的影响上，但也出现了重要的研究方向，即阐明其与胆固醇代谢和动脉粥样硬化相关的独特生理学特性。PCSK9的故事正在迅速展开，但远未结束。特别有趣的一章是PCSK9与动脉粥样硬化之间可能存在的直接联系。本综述具体从斑块生物学和炎症的实验模型、动脉粥样硬化成像研究以及观察性流行病学所产生的数据来审视这种关系。
