PCSK9: The Real Problem Behind Cholesterol

Cholesterol has earned a bad reputation over the years. However, it is required by every part of your body for day-to-day functions. In fact, cholesterol is so important to daily function, that every cell in the body can make cholesterol from basic materials, except your eyelashes! So how do you reconcile these two completely different ideas? The cholesterol that circulates in your bloodstream is the extra stuff that your body is trying to get rid of. This extra cholesterol is what can cause damage to arteries, heart disease, and increase your risk for stroke.

So, what is cholesterol? It is a type of waxy, fat-like substance, also called a lipid. Since cholesterol is fat, it can't travel alone in the bloodstream. It would end up as useless globs (imagine bacon fat floating in a pot of water). To get around this problem, the body packages cholesterol and other lipids into minuscule protein-covered particles that mix easily with blood. These tiny particles, called lipoproteins (lipid plus protein), move cholesterol and other fats throughout the body.^[1] LDL (low-density lipoprotein) is considered the “bad”, unhealthy cholesterol that can build up in the arteries and form deposits called plaques. HDL (high-density lipoprotein) is the “good”, healthy kind of cholesterol that transports excess LDL cholesterol to the liver to be removed from the body.

PCSK9 is a protein in our body that regulates the circulating levels of LDL “bad” cholesterol. Decreasing the PCSK9 proteins in the body will reduce LDL levels and reduce the risk of heart attack and stroke. There are currently two FDA-approved medications that have been very successful in blocking the PCSK9 protein once it has been made. They are Repatha and Praluent.  However, the medications are expensive and not approved for all patients under their insurance. Scientists believe it would be even more powerful to prevent the PCSK9 protein from being made in the first place. Scientists are currently studying a new class of molecules called antisense oligonucleotides (ASO).  ASOs are pieces of DNA that short-circuit the production of PCSK9, resulting in reduced LDL levels and associated risks.

Reference:

https://www.health.harvard.edu/heart-health/how-its-made-cholesterol-production-in-your-body