Loss of Plasma Proprotein Convertase Subtilisin/Kexin 9 (PCSK9) After Lipoprotein Apheresis
Rationale: Lipoprotein apheresis (LA) reduces low-density lipoprotein (LDL) levels in patients with severe Familial Hypercholesterolemia (FH). We have recently reported that more than 30% of plasma Proprotein Convertase Subtilisin/Kexin 9 (PCSK9) is bound to LDL, thus we predicted that LA would also reduce plasma PCSK9 levels by removing LDL.
Objective: Pre- and post-apheresis plasma from six FH patients on three consecutive treatment cycles was used to determine changes in PCSK9 levels.
Methods and Results: LA drastically reduced plasma LDL (by 77±4%). Concomitantly, PCSK9 levels fell by 52±5%, strongly correlating with the LDL drop (p=0.0322, r2=0.26), but not with decreases in triglyceride (49±13%) or HDL levels (18±2%). Levels of albumin, creatinine, and CK-MB did not show significant changes after LA. Similar to LDL, PCSK9 levels returned to pre-treatment values between cycles (2-week intervals). Fractionation of pre- and post-apheresis plasma showed that 81±11% of LDL-bound PCSK9 and 48±14% of apoB-free PCSK9 were removed. Separation of whole plasma, purified LDL, or the apoB-free fraction through a scaled-down, experimental dextran-sulfate cellulose beads column produced similar results.
Conclusions: Our results show for the first time that modulation of LDL levels by LA directly affect plasma PCSK9 levels, and suggest that PCSK9 reduction is an additional benefit of LA. Since the loss of PCSK9 could contribute to the LDL-lowering effect of LA, then: 1. Anti-PCSK9 therapies may reduce frequency of LA in patients currently approved for therapy, and 2. LA and anti-PCSK9 therapies may be used synergistically to reduce treatment burden.
- Received September 19, 2013.
- Revision received October 7, 2013.
- Accepted October 11, 2013.