Melendez Quantil M, Krishnaji Sreevidhya T, Wooten Catherine J, Lopez Dayami
Department of Pharmaceutical Sciences, Biomanufacturing Research Institute and Technology Enterprise (BRITE), College of Arts and Sciences, North Carolina Central University, Durham, NC 27707, USA.
Indian Institute of Science Education and Research, Bhopal, Madhya Pradesh, India.
Arch Biochem Biophys. 2017 Jul 1;625-626:39-53. doi: 10.1016/j.abb.2017.06.001. Epub 2017 Jun 3.
Heart disease ends the life of more people than any other disease in the United States. High levels of low density lipoprotein (LDL)-cholesterol cause heart diseases by increasing the formation of atherosclerotic plaques. Proprotein convertase subtilisin/kexin-9 (PCSK9) indirectly regulates plasma LDL levels by controlling the LDL receptor expression at the plasma membrane. PCSK9 also appears to modulate glucose intolerance, insulin resistance, abdominal obesity, inflammation, and hypertension. The magnitude of PCSK9's involvement in the onset of these metabolic abnormalities appears to be associated with age, sex, and ethnic background. Another regulator, the inducible degrader of the LDL receptor (IDOL), works by enhancing the ubiquitination of the LDL receptor. Herein, we will review the functions and regulatory mechanisms of PCSK9. The effects of PCSK9 on the LDL receptor, the relationship of this convertase with IDOL, and treatments currently available against hypercholesterolemia are also discussed.
在美国，心脏病导致的死亡人数比其他任何疾病都多。高水平的低密度脂蛋白（LDL）胆固醇通过增加动脉粥样硬化斑块的形成而引发心脏病。前蛋白转化酶枯草杆菌蛋白酶/kexin-9（PCSK9）通过控制质膜上LDL受体的表达间接调节血浆LDL水平。PCSK9似乎还能调节葡萄糖不耐受、胰岛素抵抗、腹部肥胖、炎症和高血压。PCSK9参与这些代谢异常发生的程度似乎与年龄、性别和种族背景有关。另一种调节因子，LDL受体的诱导降解物（IDOL），通过增强LDL受体的泛素化起作用。在此，我们将综述PCSK9的功能和调节机制。还讨论了PCSK9对LDL受体的影响、这种转化酶与IDOL的关系以及目前针对高胆固醇血症的治疗方法。
