High-Density Lipoprotein Cholesterol: The Good Cholesterol

What is high-density lipoprotein?

High-density lipoprotein is one of the serum proteins, a complex lipoprotein composed of lipids and proteins and the regulatory factors carried by them, also known as a1 lipoprotein. It is relatively rich in phospholipids and contains about 200 mg/dl of serum. its protein fraction is about 75% for A-Ⅰ and 20% for A-Ⅱ. Since it can export cholesterol and promote cholesterol metabolism, it is valued as an atherosclerosis prevention factor. HDL carries cholesterol in the surrounding tissues and then converts it into bile acids or excretes it directly from the intestine through bile. Arteriography has demonstrated a significant negative correlation between HDL cholesterol content and the degree of arterial lumen narrowing. Therefore, HDL is an anti-atherosclerotic plasma lipoprotein and a protective factor for coronary heart disease. It is commonly known as "vascular scavenger".

Composition of high-density lipoprotein

HDL is mainly synthesized by the liver and small intestine. The hepatic synthesis of nascent HDL is dominated by phospholipids and ApoA I. Under the action of LCAT, free cholesterol is transformed into cholesterol esters and lipoproteins into mature spherical HDL3, which is then transformed into HDL2 by LPL. HDL transports free cholesterol accumulated in peripheral tissues to various tissue cells, mainly the liver, by binding to lipoproteins or to certain macromolecules in the circulation. In fact, cholesterol reversal (RCT), which promotes the clearance of cholesterol from tissue cells and maintains the relative balance of intracellular cholesterol amount, thus limiting the development of atherosclerosis and acting as an anti-atherosclerotic agent. Golmset points out that LCAT completes the conversion of nascent discoid HDL to HDL3 and HDL2 through transesterification reactions, reducing the plasma HDL free cholesterol concentration, constitutes a concentration gradient of cholesterol flow from cell membranes to plasma lipoproteins, and reduces tissue cholesterol deposition.

Basic functions of HDL

HDL transports cholesterol from surrounding tissues and converts it into bile acids or excretes it directly from the intestine through bile. Therefore, HDL is an anti-atherosclerotic plasma lipoprotein and a protective factor for coronary heart disease. It is commonly known as the "vascular scavenger". HDL-C is a clinical test that represents the level of HDL in the blood, and is often measured directly by immunochemical precipitation, which is a relatively simple and inexpensive method.

Recently, numerous scientific studies have demonstrated that HDL is a unique lipoprotein with a clear anti-atherogenic effect, which can "suck out" cholesterol from the atherosclerotic vessel walls and transport it to the liver for metabolic removal.

Therefore, HDL has the name of "anti-atherosclerotic lipoprotein". HDL is mainly synthesized by the liver. It is composed of apolipoproteins, phospholipids, cholesterol and small amounts of fatty acids. HDL particles are small and can move freely in and out of the arterial walls, and can take in LDL, cholesterol, triglycerides and other harmful substances that are immersed in the bottom layer of the intima of the blood vessel walls and transport them to the liver for decomposition and excretion.

Classification of high-density lipoproteins

HDL is a multi-directional dispersion system and can be classified differently based on hydration density, particle size, charge and the type of apolipoprotein it constitutes.

HDLs can be classified into HDL2, HDL3 and VHDL by density gradient centrifugation, and into HDL2b, 2b, 3a, 3b, 3c by gradient gel electrophoresis, and individual HDL lipoproteins can be classified based on particle size by magnetic resonance. In addition, bidirectional gel electrophoresis is a very effective method for classifying HDL particles into lipid-depleted pre-beta1, versus pre-beta2: lipoproteins and mature a-HDL-containing spherical cholesterol esters.

The method of classifying HDL based on the different constitutive apolipoproteins also provides an important contribution to further understanding of HDL function and its metabolism. Lipoprotein (Lp)A-I and LpA-I:A-II are the two most abundant proteins in HDL, whereas LpE and LpE:A-I,Be lJ are the most important smaller lipoproteins in HDL.

HDL: the key to prolonging human life

As early as 1975, some foreign medical journals, published a bean curd type article, a small space recorded a scientific research results - "Dr. Miller of the United States discovered the function and mechanism of action of the anti-atherosclerotic factor HDL" The article stated that Dr. Miller and his research team had found eight cases of patients with normal lipid levels who had severe coronary heart disease (CHD is a representative disease of cardiovascular disease); and at the same time, they found that all eight cases of CHD patients had low HDL.

At that time, this article did not attract much attention, but from a modern point of view, it is simply a bombshell news, because it shows that coronary heart disease is not always triggered by high blood lipids, and that lower HDL levels may also be an important or even a key cause of coronary heart disease. And it is possible that from now on people will find a fundamental way to solve coronary heart disease and cardiovascular disease. The "lipid infiltration theory", which has ruled the lipid metabolism theory for decades, has been severely challenged.

It was not until 1985 that Drs. Brown and Gustin in the United States developed a new perspective on the mechanism of lipoprotein metabolism: an inherent apolipoprotein in human blood, high-density lipoprotein (HDL), is able to drive the reverse transport of cholesterol, and through this reverse transport, "blood waste" such as excess cholesterol in blood and tissues is carried through the liver to be broken down and reversed. "HDL also has many functions such as reversing endothelial dysfunction, stimulating prostacyclin production (which has vasodilating and antithrombotic effects), inhibiting endothelial cell apoptosis, reducing platelet aggregation, and inhibiting LDL oxidation.

This theory laid the theoretical foundation of lipoprotein metabolism, and the importance of HDL in the organism was, again, brought to a very important position.

Due to the outstanding contribution of these two doctors, they were awarded the Nobel Prize in Medicine in that year. The deep scientific mystery and the lustrous social honor beneath the theory immediately attracted many people, and various researches were carried out almost simultaneously in all continents of the world, and HDL became a bright pearl on the top of Mount Everest.

The discovery of HDL metabolic theory is an atomic bomb in the world medical history, his explosive force and shock wave, rippling for decades, many people have devoted their lives to this, because we all know clearly - who can significantly raise HDL, who will solve the problem of coronary heart disease or even the entire cardiovascular disease, who will be able to human life expectancy by decades in theory.

HDL is composed of proteins, lipids, and the regulatory factors they carry, and its protein components include apolipoproteins, enzymes, lipid transfer proteins, acute phase response proteins, complement components, and other protein components. ApoA-I regulates RCT and inflammatory responses by interacting with cell membrane receptors and activating lecithincholesterol acyltransferase (LCAT). In addition, apoA-I, apolipoprotein M (ApoM), and paraoxonase (PON) antagonize the oxidation of low density lipoprotein (LDL) and reduce foam cell production.

HDL lipid components include phospholipids, sphingolipids, neutral lipids, and fatty acids. The sphingolipids in HDL are classified as sphingolipids, ceramides, glycosylated sphingolipids, hemolytic sphingolipids, gangliosides, and thiolipids.

In mice injected with recombinant HDL consisting of sphingolipids and apoA-I mimetic peptide 5A and oleoyl phosphatidylcholine, it was observed that recombinant HDL mice had increased cholesterol efflux, reduced AS plaques, and decreased expression of AS-related pathogenic factors compared with control mice.

The diversity of HDL components determines the complexity of its function. Therefore, elucidating the mechanism of HDL components on its anti-AS ability will be helpful to find effective targets for AS prevention and treatment.

Role of HDL

1、HDL is the "lipid scavenger" in blood vessels
It is proved that the excess lipids in blood are metabolized by HDL. HDL can transfer the excess cholesterol in blood to the liver, where it is broken down into bile acid salts and excreted through the biliary tract, thus forming a special pathway for lipid metabolism, or "reverse transport pathway". Therefore, HDL can enhance lipid metabolism, keep blood vessels open, and make them cleaner, without any damage to blood vessels, safe and stable, and is the only true "scavenger" of lipids in blood vessels recognized by the international medical community.

2、HDL-"anti-atherosclerosis factor"

(1) HDL has antioxidant effect, which can protect LDL, one of the risk factors of coronary heart disease, from oxidation (because only oxidized LDL has a strong role in forming blood scale and causing atherosclerosis of arteries), and reduce or stop the damage of LDL to endothelial cells of blood vessels.

(2) Since HDL is small in size, it can penetrate the intima of arteries, break the cholesterol and other lipid plaques deposited inside and carry them to the bleeding vessel wall, and repair the broken intima, restore the function of vascular endothelial cells, so as to subside the atherosclerotic plaques quickly and restore and protect the vascular elasticity to the greatest extent, so it is called "anti-atherosclerotic factor This is why it is called "anti-atherosclerotic factor".

(3) HDL-"longevity factor"
Medical experts in the United States found that families with genetically high HDL can almost avoid atherosclerosis, much less the occurrence of cardiovascular disease, and longevity has become a common phenomenon, so it is called the "longevity factor."

(4) HDL - "good cholesterol", which is like a garbage truck that cleans up waste. It is responsible for transporting lipid waste such as cholesterol from the blood or blood vessel walls to the liver, where it is broken down and eliminated from the body. High levels of HDL cholesterol significantly reduce the risk of cardiovascular disease.

(5) HDL-"protective factor for coronary heart disease"
Studies have shown that HDL enhances the stability of pre-existing lipid plaques in blood vessels, inhibits plaque rupture or dislodgement to block blood vessels, and reduces the chance of coronary heart disease.
The protective mechanism of HDL against coronary heart disease

(6) Epidemiological surveys have shown that
When HDL<0.907mmol/L, the risk of coronary heart disease is 8 times higher than that when HDL>1.68; for every 0.5 increase in HDL, the incidence of coronary heart disease decreases by 50%. When the HDL content in blood is high, the clearance speed of lipid and blood scale is greater than the deposition speed. and blood scale clearing speed is less than the deposition speed, lipids increase, deposition accelerates, sclerosis gradually aggravates, and lesions are bound to occur.
World Health Organization (WHO) research confirms that an increase of 1 mg of HDL per 100 ml of blood can reduce the morbidity and mortality of cardiovascular diseases caused by atherosclerosis by 3-4%, and the World Health Organization (WHO) expert group declares that for cardiovascular diseases, the most important protective factor that is widely accepted and least controversial is the higher the HDL content in the body, the better!

Clinical significance of HDL

HDL physiologically acts as a carrier of cholesterol from extrahepatic tissues to the liver, thus preventing the deposition of free cholesterol on extrahepatic tissue cells. HDL cholesterol is an important reference indicator for the clinical diagnosis of coronary heart disease. Its elevation is one of the protective factors against clinical coronary heart disease and prevents and delays the development of atherosclerosis
A decrease in HDL cholesterol in serum predicts the appearance of coronary heart disease. Both HDL and total serum cholesterol are often measured clinically and their ratio is used as an informative indicator of coronary artery disease.

Impact of HDL on atherosclerosis

Epidemiological data have shown that elevated HDL concentrations have a preventive effect against the development of atherosclerotic AS. For this reason, many hypotheses have been proposed for the mechanism of HDL prevention of AS, and one commonly accepted hypothesis is the reverse cholesterol transport hypothesis. This hypothesis suggests that HDL, as a cholesterol acceptor, mediates the efflux of cholesterol from the intima of the arterial wall and transports it to the liver for metabolism by interacting with the receptor, thus reducing plasma cholesterol levels and preventing the development of AS. In addition to the reverse cholesterol transport hypothesis, many studies have shown that HDL may also prevent AS by inhibiting LDL oxidation, participating in the reverse transport of oxidized LDL, reducing oxidized LDL-induced injury, inhibiting monocyte adhesion and migration to the intima, stimulating endothelial cell repair and proliferation, and inhibiting growth factor-induced proliferation of vascular smooth muscle cells. In conclusion, the mechanism of action of HDL in preventing AS is quite complex and is the result of the interaction of multiple factors.

References：

1. High-density lipoprotein - Wikipedia

See also:

1. Cholesterol care