College of Pharmacy and Pharmaceutical Sciences, Institute of Public Health, Florida A&M University, Davie, FL, 33324, USA.
Memorial Regional Hospital-Department of Pharmacy, 3501 Johnson Street, Hollywood, FL, 32301, USA.
Am J Cardiovasc Drugs. 2021 May;21(3):255-265. doi: 10.1007/s40256-020-00437-7.
Lipoprotein(a) is a unique form of low-density lipoprotein. It is associated with a high incidence of premature atherosclerotic disease such as coronary artery disease, myocardial infarction, and stroke. Plasma levels of this lipoprotein and its activities are highly variable. This is because of a wide variability in the size of the apolipoprotein A moiety, which is determined by the number of repeats of cysteine-rich domains known as "kringles." Although the exact mechanism of lipoprotein(a)-induced atherogenicity is unknown, the lipoprotein has been found in the arterial walls of atherosclerotic plaques. It has been implicated in the formation of foam cells and lipid deposition in these plaques. Pharmacologic management of elevated levels of lipoprotein(a) with statins, fibrates, or bile acid sequestrants is ineffective. The newer and emerging lipid-lowering agents, such as the second-generation antisense oligonucleotides, cholesteryl ester transfer protein inhibitors, and proprotein convertase subtilisin/kexin type 9 inhibitors offer the most effective pharmacologic therapy.
脂蛋白(a)是一种独特的低密度脂蛋白形式。它与冠心病、心肌梗死和中风等早发性动脉粥样硬化疾病的高发病率有关。这种脂蛋白及其活性的血浆水平高度可变。这是因为载脂蛋白 A 部分的大小存在广泛的可变性，这是由称为“kringles”的富含半胱氨酸结构域的重复次数决定的。尽管脂蛋白(a)引起动脉粥样硬化的确切机制尚不清楚，但已在动脉粥样硬化斑块的动脉壁中发现了脂蛋白(a)。它与泡沫细胞的形成和这些斑块中的脂质沉积有关。用他汀类药物、贝特类药物或胆汁酸螯合剂对脂蛋白(a)水平升高进行药物治疗效果不佳。较新的和新兴的降脂药物，如第二代反义寡核苷酸、胆固醇酯转移蛋白抑制剂和前蛋白转化酶枯草溶菌素/激肽释放酶 9 抑制剂，提供了最有效的药物治疗。
