PCSK9 Inhibitors Improve Atherosclerosis, CVD via Immunity

The inhibition of proprotein convertase subtilisin kexin 9 (PCSK9) could help improve atherosclerosis and, in turn, improve cardiovascular disease in a way that is unrelated to the lowering of low-density lipoprotein (LDL) cholesterol, according to a recent study.

Findings were presented on August 28, 2017, by Dr Johan Frostegård at the European Society of Cardiology Congress in Barcelona, Spain.
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T-cells and dendritic cells are commonly found in atherosclerotic plaques, and the activation of these immune cells in atherosclerosis patients may play a major role in developing cardiovascular disease. However, little is known about the effects of PCSK9 on the maturation of dendritic cells and the activation of T-cells.

In their study, the researchers assessed patients with atherosclerotic plaques undergoing carotid endarterectomy in order to examine how PCSK9 affects the induction of dendritic cell maturation and T-cell activation via oxidized LDL. T-cells were obtained via carotid arteries and the peripheral blood of healthy individuals. Human peripheral blood monocytes were then differentiated into dendritic cells, which were pretreated with oxidized LDL and subsequently co-cultured with T-cells.
Results indicated that oxidized LDL promoted the maturation of dendritic cells, which aided in the activating T-cells into T helper cells. The researchers also found that oxidized LDL induced PCSK9. Ultimately, silencing the PCSK9 gene reversed the effects of oxidized LDL on dendritic cells and T-cells and repressed both types of cells.

“Our study suggests that the benefits of PCSK9 inhibition extend beyond lowering LDL cholesterol,” Frostegård concluded. “Here we show that PCSK9 inhibition has a novel immunological role in the maturation and activation of dendritic cells and T-cells by oxidized LDL, a central player in atherosclerosis. This creates an anti-inflammatory state which may directly influence atherosclerosis and cardiovascular disease, independent of LDL-lowering.”

—Christina Vogt

Reference:

PCSK9 inhibition could ameliorate cardiovascular disease by immune mechanisms [press release]. Barcelona, Spain: European Society of Cardiology; August 28, 2017. https://www.escardio.org/The-ESC/Press-Office/Press-releases/PCSK9-inhibition-could-ameliorate-cardiovascular-disease-by-immune-mechanisms. Accessed August 28, 2017.