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.
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.