From the South Australian Health and Medical Research Institute, Adelaide, Australia (E.J.A.).
The University of Adelaide, Australia (E.J.A.).
Arterioscler Thromb Vasc Biol. 2019 Oct;39(10):1902-1910. doi: 10.1161/ATVBAHA.119.311574. Epub 2019 Aug 29.
Vascular calcification (VC) is strongly associated with all-cause mortality and is an independent predictor of cardiovascular events. Resulting from its complex, multifaceted nature, targeted treatments for VC have not yet been developed. Lipoproteins are well characterized in the pathogenesis of atherosclerotic plaques, leading to the development of plaque regressing therapeutics. Although their roles in plaque progression are well documented, their roles in VC, and calcification of a plaque, are not well understood. In this review, early in vitro data and clinical correlations suggest an inhibitory role for HDL (high-density lipoproteins) in VC, a stimulatory role for LDL (low-density lipoprotein) and VLDL (very low-density lipoprotein) and a potentially causal role for Lp(a) (lipoprotein [a]). Additionally, after treatment with a statin or PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor, plaque calcification is observed to increase. With the notion that differing morphologies of plaque calcification associate with either a more stable or unstable plaque phenotype, uncovering the mechanisms of lipoprotein-artery wall interactions could produce targeted therapeutic options for VC.
血管钙化（VC）与全因死亡率密切相关，是心血管事件的独立预测因子。由于其复杂的、多方面的性质，针对 VC 的靶向治疗尚未开发。脂蛋白在动脉粥样硬化斑块的发病机制中得到了很好的描述，导致了斑块消退治疗的发展。尽管它们在斑块进展中的作用已有充分的记录，但它们在 VC 中的作用，以及斑块的钙化，还没有得到很好的理解。在这篇综述中，早期的体外数据和临床相关性表明 HDL（高密度脂蛋白）在 VC 中具有抑制作用，LDL（低密度脂蛋白）和 VLDL（极低密度脂蛋白）具有刺激作用，Lp(a)（脂蛋白[a]）具有潜在的因果作用。此外，在用他汀类药物或 PCSK9（前蛋白转化酶枯草溶菌素/克氏蛋白酶 9）抑制剂治疗后，观察到斑块钙化增加。由于不同形态的斑块钙化与更稳定或不稳定的斑块表型相关，揭示脂蛋白-动脉壁相互作用的机制可能为 VC 提供靶向治疗选择。
