High density lipoproteins represent one of several classes of transport molecules that carry cholesterol esters and other lipophilic substances in blood plasma. HDLs handle the transport of excess cholesterol from tissues to the liver. In contrast to low-density lipoproteins, which are responsible for the opposite transport of cholesterol, HDLs are also called “good” cholesterols because, for example, they absorb and remove excess cholesterol from vessel walls.
What are high-density lipoproteins?
High density lipoproteins (HDL) are composed of about half proteins and half cholesterol esters, triglycerides, and phospholipids. They can be further divided into four subclasses. The proteins consist mainly of so-called amphiphilic apolipoproteins (ApoLp). As high-density lipoproteins, they form one of five classes. The other lipoprotein classes are low density (LDL), very low density (VLDL), intermediate density lipoproteins (IDL), chylomicrons, and lipoprotein a (Lp(a)). Lipoproteins of all classes are ultimately transport molecules that move water-insoluble lipophilic substances such as cholesterol esters in blood plasma to or from target organs. Lipoproteins with a density of 1.063 to 1.210 g/l are classified as HDLs. The molecules reach a size of only 5 to 17 nanometers. The structure and size of HDLs vary depending on cholesterols, lipids and triglycerides transported by the HDL molecule. The class of HDLs is considered beneficial from a physiological-medical point of view because cholesterols and other substances are taken up from certain tissues and transported to the liver, thus improving atherosclerotic plaques (calcifications) in blood vessels, which consist mainly of deposited cholesterols. In contrast, LDLs transport cholesterols from the liver to target tissues, including the walls of blood vessels. In principle, therefore, HDLs are referred to as physiologically beneficial and LDLs as physiologically unfavorable (“evil”).
Function, effects, and roles
Cholesterols have an enormously high and central importance for body metabolism. They are a necessary component of all cell membranes, including the epithelia in blood vessels. In addition, cholesterols fulfill important functions in the brain. Low cholesterol is associated with reduced cognitive and other brain functions. However, tiny injuries and tears in blood vessels can lead to the triggering of an excessive repair process, resulting in the formation of plaques in the vessels that can lead to atherosclerotic narrowing and loss of elasticity of certain blood vessels. Because a high proportion of plaques in the vessels are made up of cholesterol, high cholesterol levels have for decades been thought to be harmful to health. In this context, HDL has a positive role as a transport molecule, since it transports excess cholesterol from the tissues to the liver, where it is further metabolized, i.e. broken down or recycled. In contrast, the main task and function of the LDL fraction of lipoproteins is to transport cholesterol from the liver to the target tissue. The reverse transport of excess cholesterol performed by HDL is also called reverse cholesterol transport. A high level of HDL in blood serum is considered to reduce the risk of coronary heart disease. In addition, atherosclerotic plaques may even regress, and HDLs are associated with antipoptotic and antithrombotic effects.
Formation, occurrence, properties, and optimal values
The concentration of cholesterol in the body cannot be measured directly; it can only ever be measured indirectly by determining lipoproteins and triglycerides in blood serum. Because of the central importance of cholesterol for a large number of metabolic processes, the body is able to regulate the concentration of the individual lipoprotein classes itself via synthesis processes largely independently of the food supplied. The starting point for biosynthesis is the so-called mevalonate pathway, through which DMAPP (dimethylallyl pyrophosphate) is formed. DMAPP is mainly used in the liver, but also in the intestinal epithelium, to synthesize cholesterol in an 18-step process. Because the lipoprotein molecules are too large to pass the blood-brain barrier, the brain is able to produce the required cholesterol itself.The concentration of HDL in blood serum seems to largely follow genetic predisposition in conjunction with life circumstances. After decades of demonizing a high level of lipoproteins, the focus is increasingly on the concentration of HDLs, on the assumption that HDLs transport excess cholesterol from the membranes of the blood vessels to the liver and thus counteract atherosclerotic vascular changes and all subsequent damage. The LDL to HDL ratio is also considered important. A ratio of less than three is considered positive, while ratios above 4 are considered unfavorable. Also independent of the LDL to HDL ratio, a concentration of HDL less than 40 ml/dl is considered unfavorable and a value greater than 60 is considered favorable.
Diseases and disorders
A low blood serum HDL level of less than 40 ml/dl increases the risk that atherosclerotic changes will occur in the blood vessels because the HDLs cannot adequately perform their task of removing excess cholesterol. This increases the risk of further consequential damage such as high blood pressure, heart attack and stroke. Unilaterally reduced HDL synthesis can be caused by the rare Tangier disease. The genetic defect causes a disruption in the protein apolipoprotein A1 (ApoA1), which is needed to release excess cholesterol from tissues and attach it to HDL. The disease is inherited in an autosomal recessive manner, so it affects both men and women. Diseases such as diabetes type 2, also lead to a reduction in HDL levels. In addition to genetic predisposition, life circumstances also influence the concentration of HDLs in the blood serum. Lack of exercise, smoking and obesity have a negative, i.e. lowering, influence on the HDL level. This means that if the concentration of HDL is too low, normalization of body weight and an increase in physical activity have a positive, i.e., increasing, influence on HDL concentration.
