Physical activity to reduce PCSK9 levels

Abstract

The amount of physical activity (PA) people practice everyday has been reducing in the last decades. Sedentary subjects tend to have an impaired lipid plasma profile with a higher risk of atherosclerosis and related cardio- and cerebrovascular events. Regular PA helps in both primary and secondary cardiovascular prevention because of its beneficial effect on the whole metabolism. Several studies reported lower levels of plasma lipids in trained subjects, but the precise mechanisms by which PA modulates lipoproteins remain only partially described. Thereupon, proprotein convertase subtilisin/kexin type 9 (PCSK9) is a serin protease whose main function is to reduce the amount of low-density lipoprotein cholesterol (LDL-C) receptors, with the direct consequence of reducing LDL-C uptake by the liver and increasing its circulating pool. Accordingly, recently developed PCSK9 inhibitors improved cardiovascular prevention and are increasingly used to reach LDL-C goals in patients at high CV risk. Whether PA can modulate the levels of PCSK9 remains partially explored. Recent studies suggest PA as a negative modulator of such a deleterious CV mediator. Yet the level of evidence is limited. The aim of this review is to summarize the recent reports concerning the regulatory role of PA on PCSK9 plasma levels, highlighting the beneficial role of regular exercise on the prevention of atherosclerosis and overall CV health.

Keywords: cardiovascular; exercise; inflammation; physical activity; proprotein convertase subtilisin/kexin type 9.

Figure 1

Evidence suggest that regular physical activity can regulate the PCSK9 plasma levels even though few evidence is available at the moment. As possible explanations, the reduction of resistin, annexin A2, and LOX-1 are reported with the most concrete results. Although, PCSK9 can be also augmented in trained subjects. This is probably related to a higher metabolism, a possible undiscovered mechanism, or confounding factors. While it is less known if exercise training affects the plasma levels of SREBP2, both fasting and statin treatment represent two confounding factors when evaluating the possible role of physical activity on PCSK9 levels. LOX-1, lectin-type oxidized low-density lipoprotein receptor-1; Proprotein convertase subtilisin/kexin type 9; SREBP2, sterol regulatory element-binding protein 2.