Department of Surgery, School of Clinical Sciences, Monash Health, Clayton, Australia (Z.S.Y.L.).
From the Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA (A.N.L.).
Arterioscler Thromb Vasc Biol. 2019 Apr;39(4):613-622. doi: 10.1161/ATVBAHA.118.311577.
Inflammatory cytokines are necessary for an acute response to injury and the progressive healing process. However, when this acute response does not resolve and becomes chronic, the same proteins that once promoted healing then contribute to chronic inflammatory pathologies, such as atherosclerosis. OPN (Osteopontin) is a secreted matricellular cytokine that signals through integrin and CD44 receptors, is highly upregulated in acute and chronic inflammatory settings, and has been implicated in physiological and pathophysiologic processes. Evidence from the literature suggests that OPN may fit within the Goldilocks paradigm with respect to cardiovascular disease, where acute increases are protective, attenuate vascular calcification, and promote postischemic neovascularization. In contrast, chronic increases in OPN are clinically associated with an increased risk for a major adverse cardiovascular event, and OPN expression is a strong predictor of cardiovascular disease independent of traditional risk factors. With the recent finding that humans express multiple OPN isoforms as the result of alternative splicing and that these isoforms have distinct biologic functions, future studies are required to determine what OPN isoform(s) are expressed in the setting of vascular disease and what role each of these isoforms plays in vascular disease progression. This review aims to discuss our current understanding of the role(s) of OPN in vascular disease pathologies using evidence from in vitro, animal, and clinical studies. Where possible, we discuss what is known about OPN isoform expression and our understanding of OPN isoform contributions to cardiovascular disease pathologies.
炎症细胞因子对于损伤的急性反应和进行性愈合过程是必要的。然而，当这种急性反应没有得到解决并变成慢性时，曾经促进愈合的相同蛋白质会导致慢性炎症性病理，如动脉粥样硬化。OPN（骨桥蛋白）是一种分泌的基质细胞因子，通过整合素和 CD44 受体传递信号，在急性和慢性炎症环境中高度上调，并与生理和病理生理过程有关。文献中的证据表明，OPN 可能符合心血管疾病中的“金发姑娘”模式，即急性增加具有保护作用，可减轻血管钙化，并促进缺血后新生血管形成。相比之下，慢性 OPN 增加与发生主要不良心血管事件的风险增加相关，并且 OPN 表达是独立于传统危险因素的心血管疾病的强烈预测因子。最近发现，人类由于选择性剪接而表达多种 OPN 同工型，并且这些同工型具有不同的生物学功能，因此需要进一步研究以确定在血管疾病的背景下表达哪种 OPN 同工型，以及这些同工型中的每一种在血管疾病进展中起什么作用。这篇综述旨在使用来自体外、动物和临床研究的证据，讨论我们目前对 OPN 在血管疾病病理中的作用的理解。在可能的情况下，我们讨论了已知的 OPN 同工型表达情况以及我们对 OPN 同工型对心血管疾病病理的贡献的理解。
