From the Guidelines
The Protein Kinase 9 (PK9) receptor is not directly mentioned in the provided evidence, however, the Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) is extensively discussed, which might be the point of confusion. Based on the most recent and highest quality study available, the PCSK9 receptor plays a crucial role in regulating LDL-C levels by binding to the LDL receptor (LDL-R) and promoting its degradation, thereby reducing the number of LDL-R on the surface of hepatocytes and increasing LDL-C levels in the circulation 1. The evidence suggests that individuals with PCSK9 loss-of-function mutations have increased numbers of LDL-R on the surface of their hepatocytes, leading to robust LDL-C clearance from the circulation and a significant reduction in cardiovascular events over long-term follow-up 1. Key points to consider:
- PCSK9 inhibitors, such as evolocumab and alirocumab, have been shown to reduce LDL-C levels by 59% and 36-59%, respectively, and decrease the risk of major adverse cardiovascular events (MACE) by 15-20% 1.
- The FOURIER trial demonstrated that evolocumab reduced LDL-C levels by 59% and decreased the risk of MACE by 15% compared to placebo 1.
- The ODYSSEY OUTCOMES trial showed that alirocumab reduced LDL-C levels by 36-59% and decreased the risk of MACE by 15% compared to placebo 1. It is essential to note that the provided evidence does not support the existence of a PK9 receptor, and the discussion is focused on the PCSK9 receptor. In clinical practice, the use of PCSK9 inhibitors should be guided by the patient's individual risk profile and the potential benefits and risks of treatment.
From the Research
Definition and Role of PK9 Receptor
- The PK9 receptor is not directly mentioned in the provided studies, but based on the context, it appears to refer to the Protein Kinase 9 (PK9) in Plasmodium parasites.
- According to the study 2, PfPK9 (Plasmodium falciparum protein kinase 9) is an atypical protein kinase that phosphorylates the Plasmodium E2 ubiquitin-conjugating enzyme PfUBC13, mediating K63-linkage-specific polyubiquitination.
- The role of PK9 in Plasmodium parasites is to regulate parasite development, and its inhibition can promote the growth of liver-stage parasites 2.
Comparison with PCSK9
- It's worth noting that the provided studies mainly discuss PCSK9 (proprotein convertase subtilisin/kexin type 9), which is a different protein from PK9.
- PCSK9 is a serine protease that plays a pivotal role in the reduction of the number of low-density lipoprotein receptors (LDLRs) on the surface of hepatocytes, leading to an increase in the level of cholesterol in the blood 3, 4, 5, 6.
- While PK9 and PCSK9 are distinct proteins, they both play important roles in their respective biological contexts, with PK9 involved in parasite development and PCSK9 involved in lipid metabolism.