Vaccination against cholesterol?

- Increased blood, fat and cholesterol levels are among the main risk factors for the onset of cardiovascular diseases. Therefore, besides high blood pressure drugs, statins are one of the most commonly prescribed medications worldwide. Statins inhibit the body's cholesterol synthesis and can thus help to reduce blood cholesterol levels. However, their broad usage is often controversial and widely discussed, with potential alternatives currently being researched. Presently, a focus of scientific interest is in the proprotein convertase subtilisin/kexin type 9 (PCSK9), which is considerably involved in the regulation of cholesterol metabolism. The PCSK9 binds to the LDL receptor on the liver cell surface and leads to its degradation. Because of the lowered receptor density, the proportion of LDL cholesterol taken up and broken down in the liver decreases and its concentration in the blood rises. High LDL values ​​are considered to be a separate risk factor for the development of atherosclerosis and consequently for cardiovascular diseases and stroke.

The circulating LDL can easily be oxidized by free radicals. The macrophages in the vessel walls take up the resulting oxidized LDL (OxLDL), thereby transforming themselves into so-called foam cells. The formation of foam cells, and the subsequent inflammation and reorganization processes, influence the genesis of atherosclerosis.

Accordingly, the inhibition of PCSK9 is considered a possible alternative to using statins. Recently, the European Heart Journal published promising study results in regards to this issue. The researchers investigated the activity of a vaccine called AT04A in mice, which led to the formation of specific antibodies against PCSK9. The vaccine administration resulted in a diminishment of cholesterol levels of up to 53%. In addition, the damage in atherosclerotic vessels decreased, as well as the concentration of vascular inflammatory markers. Moreover, the generated antibodies were still detectable for up to one year after vaccination, in the blood of the mice. In contrast, the PCSK9 inhibitors already available on the market must be injected twice a week.

In a second study from the Medical University of Vienna, the vaccine is already being tested on humans. The completion of the study and results are expected by the end of 2017. The PCSK9 currently appears to be a promising target in cholesterol metabolism. Alongside the already available antibodies, further mechanisms for influencing PCSK9 and lowering LDL cholesterol levels are being researched. So, in the near future, a wide range of effective drugs for large-scale use could be available - medicines that could supplement statins, or replace them altogether.

Image 1  © “andreysafonov” / Fotolia.com

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