Cholesteryl ester transfer protein, or CETP, is a protein found in human plasma that plays a role in how the body processes fats. It is involved in the balance and movement of lipids throughout the bloodstream. Maintaining a healthy balance of these fats is important for overall well-being.
What is CETP and How Does It Work?
CETP is a plasma protein that acts as a shuttle for lipids within the bloodstream. Its main function is to facilitate the exchange of cholesteryl esters and triglycerides between different lipoprotein particles. Specifically, CETP moves cholesteryl esters from high-density lipoprotein (HDL) particles to triglyceride-rich lipoproteins, such as very-low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) particles. In return, triglycerides are transferred from VLDL and LDL back to HDL.
This exchange process is part of the body’s lipid metabolism, particularly in a pathway called reverse cholesterol transport. Reverse cholesterol transport involves HDL particles picking up excess cholesterol from peripheral tissues and transporting it back to the liver for removal. CETP’s activity influences how cholesterol is redistributed among these lipoprotein particles during this transport.
How CETP Affects Your Cholesterol
The activity of CETP directly impacts the levels of different types of cholesterol in the blood. When CETP activity is high, it can lead to lower levels of HDL cholesterol, often referred to as “good” cholesterol. This occurs because CETP transfers cholesteryl esters out of HDL particles.
Conversely, higher CETP activity can contribute to increased levels of LDL cholesterol, known as “bad” cholesterol, and triglycerides. This shift in lipid distribution can disrupt the delicate balance of cholesterol in the bloodstream. Lower CETP activity, on the other hand, results in higher HDL cholesterol levels, which is beneficial for maintaining healthy cholesterol balance.
The Link Between CETP and Heart Disease
The influence of CETP on cholesterol levels has led to research into its connection with cardiovascular diseases like atherosclerosis and heart attacks. Atherosclerosis is a condition where plaque builds up inside the arteries, narrowing them and increasing the risk of heart events. Altered CETP activity, by affecting HDL and LDL levels, can influence this plaque buildup.
Variations in the gene that produces CETP have been studied in relation to an individual’s risk of heart disease. For example, some genetic variations that lead to lower CETP activity are associated with higher HDL levels, which offer protection against cardiovascular issues. Conversely, higher CETP activity, by promoting lower HDL and higher LDL, contributes to an increased risk of heart disease.
CETP Inhibitors as a Medical Strategy
Given CETP’s role in cholesterol metabolism, drugs designed to inhibit its activity have been developed as a medical strategy. The aim of these CETP inhibitors is to increase HDL cholesterol levels and lower LDL cholesterol, with the goal of reducing the risk of cardiovascular disease.
Several CETP inhibitors have been investigated in clinical trials, including torcetrapib, anacetrapib, dalcetrapib, and evacetrapib. The outcomes of these trials have been mixed, highlighting the complexities in targeting this pathway. While some inhibitors successfully raised HDL levels, their ability to reduce cardiovascular events has varied, indicating that simply increasing HDL cholesterol does not always translate into improved heart outcomes.