PCSK9 inhibition could ameliorate cardiovascular disease by immune mechanisms

ScienceDaily | 8/28/2017 | Staff
kims (Posted by) Level 3
T cells and dendritic cells are common in atherosclerotic plaques. Atherosclerosis is a chronic inflammatory process in which activation of these immune cells may play a major role in the development of cardiovascular disease.

Researchers at the Karolinska Institute in Stockholm, Sweden, developed an experimental system to directly study how these immune cells from human atherosclerotic plaques are activated in order to discover mechanisms and potential therapies.

Convertase - Subtilisin - Kexin - PCSK9 - LDL

Specifically, they examined proprotein convertase subtilisin kexin 9 (PCSK9), which is known to target the LDL receptor for degradation, resulting in increased LDL levels. Knowledge of this mechanism has led to the development of PCSK9 inhibitors, which lower LDL cholesterol.

In this study, researchers investigated the immune effects of PCSK9 on the induction of dendritic cell maturation and T cell activation by oxidised LDL.

T - Cells - Carotid - Arteries - Patients

T cells were isolated from the carotid arteries of patients with atherosclerotic plaques who were undergoing carotid endarterectomy to clear the blocked arteries. T cells were also obtained from the peripheral blood of healthy individuals. Human peripheral blood monocytes were differentiated into dendritic cells.

The dendritic cells were pretreated with oxidised LDL and then co-cultured with T cells from atherosclerotic plaques and from blood. The researchers studied the effects of PCSK9 and its inhibition on the...
(Excerpt) Read more at: ScienceDaily
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