Department of Biochemistry.
Robarts Research Institute, Schulich School of Medicine & Dentistry, The University of Western Ontario, London, Ontario, Canada.
Curr Opin Lipidol. 2018 Jun;29(3):259-267. doi: 10.1097/MOL.0000000000000499.
Evidence continues to mount for an important role for elevated plasma concentrations of lipoprotein(a) [Lp(a)] in mediating risk of atherothrombotic and calcific aortic valve diseases. However, there continues to be great uncertainty regarding some basic aspects of Lp(a) biology including its biosynthesis and catabolism, its mechanisms of action in health and disease, and the significance of its isoform size heterogeneity. Moreover, the precise utility of Lp(a) in the clinic remains undefined.
The contribution of elevated Lp(a) to cardiovascular risk continues to be more precisely defined by larger studies. In particular, the emerging role of Lp(a) as a potent risk factor for calcific aortic valve disease has received much scrutiny. Mechanistic studies have identified commonalities underlying the impact of Lp(a) on atherosclerosis and aortic valve disease, most notably related to Lp(a)-associated oxidized phospholipids. The mechanisms governing Lp(a) concentrations remain a source of considerable dispute.
This article highlights some key remaining challenges in understanding Lp(a) actions and clinical significance. Most important in this regard is demonstration of a beneficial effect of lowering Lp(a), a development that is on the horizon as effective Lp(a)-lowering therapies are being tested in the clinic.
越来越多的证据表明，脂蛋白(a)[Lp(a)]血浆浓度升高在介导动脉粥样硬化血栓形成和钙化性主动脉瓣疾病风险方面起着重要作用。然而，关于 Lp(a)生物学的一些基本方面仍存在很大的不确定性，包括其生物合成和分解代谢、在健康和疾病中的作用机制，以及其同型大小异质性的意义。此外，Lp(a)在临床上的确切用途仍未确定。
更大规模的研究进一步精确地定义了升高的 Lp(a)对心血管风险的贡献。特别是，Lp(a)作为钙化性主动脉瓣疾病的一个强有力的危险因素的作用受到了广泛关注。机制研究确定了 Lp(a)对动脉粥样硬化和主动脉瓣疾病影响的共同基础，最显著的是与 Lp(a)相关的氧化磷脂有关。控制 Lp(a)浓度的机制仍然存在很大争议。
本文强调了理解 Lp(a)作用和临床意义方面一些关键的遗留挑战。在这方面最重要的是证明降低 Lp(a)的有益效果，随着有效的 Lp(a)降低疗法正在临床试验中进行测试，这一发展即将成为现实。
