Blocking the Cholesterol Gene

Recent research from the Institut de Recherches Cliniques de Montréal in Canada has shown that the protein annexin A2 could potentially work in place of drugs called “statins” to reduce concentrations of cholesterol in the blood by suppressing the effects of the proprotein convertase subtilisin/kexin type 9 (PCSK9) gene. The primary carriers of cholesterol in the blood are proteins called low-density lipoproteins (LDLs). The body removes excess cholesterol through LDL receptors which sit on the surface of cells (chiefly in the liver) and bind to LDL-cholesterol particles. The PCSK9 gene synthesises a protein known to regulate cholesterol levels by breaking down these LDLRs before they reach the surface of the cell, thus increasing cholesterol concentrations. In some people with a mutation in the PCSK9 gene, the synthesised protein can become overactive resulting in hypercholesterolemia (an inherited form of high cholesterol).

Current anti-cholesterol drugs, statins, reduce production of cholesterol and increase LDLRs, but they simultaneously increase the degradation of these receptors by upping the number of PCSK9 proteins. This is where annexin A2 proteins come in, as it is able to inhibit PCSK9 meaning that it could work in conjunction with statins to improve the efficacy of the drugs, or even become a replacement for those who are unable to use statins in their current form.

Reference: Mayer G, Poirier S, and Seidah NG. (2008) Annexin A2 is a C-terminal PCSK9-binding protein that regulates endogenous low density lipoprotein receptor levels. J Biol Chem, November 14; 283(46): 31791-801
http://www.medicalnewstoday.com/articles/130748.php
Additional Information:
http://ghr.nlm.nih.gov/gene=pcsk9
http://www4.utsouthwestern.edu/moleculargenetics/pages/brown/past2.html