Review on the biology of PCSK9 in Cardiovascular Research

The group of Prof. Catapano at University of Milano, Italy (IRCCS MultiMedica-MultiMedica SpA, Cardiovascular Department, Atherosclerosis Center) published an highly interesting review on the biological processes of Proprotein Convertase Subtilisin Kexin 9 (PCSK9). PCK9 is a key regulator of low-density lipoprotein receptor levels and LDL-cholesterol levels. The PCSK9 gene is associated with hypocholesterolaemia and protection against cardiovascular disease, setting the stage for the therapeutic potential of PCSK9 inhibition as a valid therapeutic approach to manage hypercholesterolaemia and related diseases.

Morata 1 ESC

Cardiovascular diseases are the number one killer across the globe, with an estimated 17.5 million people dying from one of these disorders in 2012 — 31% of all deaths. One of the risk factors is atherosclerosis: caused when high levels of LDL cholesterol (LDL-C) in the blood build up in the inner walls of arteries, thickening them and provoking an inflammatory response, it can lead to heart attack or stroke. Levels of LDL-C are therefore often used as a surrogate marker for the risk of having a cardiovascular event.

Statins have been a mainstay of heart attack and stroke prevention for the past 20 years, but the race is on to bring a new drug to market that targets an enzyme called PCSK9. The PCSK9 protein interferes with the clearance of LDL-C from the blood. LDL receptors on liver cells remove LDL-C from the blood by binding it and then moving it into the cell for elimination. The lipid-free receptors then return to the surface of the cell. When PCSK9 binds to the LDL receptor, however, the receptor is unable to re-emerge on to the cell surface to remove more LDL-C, which then remains in the blood. By inhibiting the PCSK9 protein, PCSK9 inhibitors essentially improve the liver’s ability to recycle LDL receptors, resulting in a greater number of receptors on the cell surface and enabling more LDL-C to be removed from circulation.


Full article can be read here.

This project has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement N°667837.