Lipidology is the scientific study of lipids. Lipids are a group of biological macromolecules that have a multitude of functions in the body. [1] [2] [3] Clinical studies on lipid metabolism in the body have led to developments in therapeutic lipidology for disorders such as cardiovascular disease. [4]
Compared to other biomedical fields, lipidology was long-neglected as the handling of oils, smears, and greases was unappealing to scientists and lipid separation was difficult. [5] It was not until 2002 that lipidomics, the study of lipid networks and their interaction with other molecules, appeared in the scientific literature. [6] Attention to the field was bolstered by the introduction of chromatography, spectrometry, and various forms of spectroscopy to the field, allowing lipids to be isolated and analyzed. [5] The field was further popularized following the cytologic application of the electron microscope, which led scientists to find that many metabolic pathways take place within, along, and through the cell membrane - the properties of which are strongly influenced by lipid composition. [5]
The Framingham Heart Study and other epidemiological studies have found a correlation between lipoproteins and cardiovascular disease (CVD). [7] Lipoproteins are generally a major target of study in lipidology since lipids are transported throughout the body in the form of lipoproteins. [2]
A class of lipids known as phospholipids help make up what is known as lipoproteins, and a type of lipoprotein is called high density lipoprotein (HDL). [8] A high concentration of high density lipoproteins-cholesterols (HDL-C) have what is known as a vasoprotective effect on the body, a finding that correlates with an enhanced cardiovascular effect. [9] There is also a correlation between those with diseases such as chronic kidney disease, coronary artery disease, or diabetes mellitus and the possibility of low vasoprotective effect from HDL. [10]
Another factor of CVD that is often overlooked involves the concentrations of low-density lipoproteins (LDL) and very low-density lipoproteins (VLDL). These are often seen at higher than expected and necessary levels in the body due to food uptake, family history, and a person's metabolic rate. There is a correlation between these increased levels and stroke, heart attack, and mortality. [11]
Statins are a class of drugs used to treat cardiovascular disease by lowering lipid levels, specifically LDL-C levels. [12] Statins have shown to reduce new cardiovascular events by 30-40%. [13] However, complications may still arise even after taking the drug and some patients are statin-intolerant. Lipoprotein apheresis therapy is another nonsurgical treatment for reducing LDL-C concentrations.
PCSK9 inhibitors are a new drug that can replace statins and lipoprotein apheresis therapy. [13] For patients that are statin-intolerant, PCSK9 inhibitors can provide a therapeutic alternative.
Lipidomics is the complete profile of all lipids in a biological system at a given time. This is used to identify and quantify the lipids that can be detected. Since lipids have a variety of functions in the body, being able to understand which specific types are present in the body and at what levels is crucial to understand the diseases that result due to lipids. [14] Methods of lipidomic analysis include mass spectrometry and chromatography. [6] Monitoring lipid concentration can reveal much about an organism's health.
Cholesterol is the principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils.
High-density lipoprotein (HDL) is one of the five major groups of lipoproteins. Lipoproteins are complex particles composed of multiple proteins which transport all fat molecules (lipids) around the body within the water outside cells. They are typically composed of 80–100 proteins per particle. HDL particles enlarge while circulating in the blood, aggregating more fat molecules and transporting up to hundreds of fat molecules per particle.
Low-density lipoprotein (LDL) is one of the five major groups of lipoprotein that transport all fat molecules around the body in extracellular water. These groups, from least dense to most dense, are chylomicrons, very low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), low-density lipoprotein (LDL) and high-density lipoprotein (HDL). LDL delivers fat molecules to cells. LDL has been associated with the progression of atherosclerosis.
Atherosclerosis is a pattern of the disease arteriosclerosis, characterized by development of abnormalities called lesions in walls of arteries. This is a chronic inflammatory disease involving many different cell types, and driven by elevated levels of cholesterol in the blood. These lesions may lead to narrowing of the arterial walls due to buildup of atheromatous plaques. At onset there are usually no symptoms, but if they develop, symptoms generally begin around middle age. In severe cases, it can result in coronary artery disease, stroke, peripheral artery disease, or kidney disorders, depending on which body part(s) the affected arteries are located in the body.
A lipoprotein is a biochemical assembly whose primary function is to transport hydrophobic lipid molecules in water, as in blood plasma or other extracellular fluids. They consist of a triglyceride and cholesterol center, surrounded by a phospholipid outer shell, with the hydrophilic portions oriented outward toward the surrounding water and lipophilic portions oriented inward toward the lipid center. A special kind of protein, called apolipoprotein, is embedded in the outer shell, both stabilising the complex and giving it a functional identity that determines its role.
Statins are a class of medications that reduce illness and mortality in people who are at high risk of cardiovascular disease.
Lipid-lowering agents, also sometimes referred to as hypolipidemic agents, cholesterol-lowering drugs, or antihyperlipidemic agents are a diverse group of pharmaceuticals that are used to lower the level of lipids and lipoproteins, such as cholesterol, in the blood (hyperlipidemia). The American Heart Association recommends the descriptor 'lipid lowering agent' be used for this class of drugs rather than the term 'hypolipidemic'.
Hypercholesterolemia, also called high cholesterol, is the presence of high levels of cholesterol in the blood. It is a form of hyperlipidemia, hyperlipoproteinemia, and dyslipidemia.
Dyslipidemia is a metabolic disorder characterized by abnormally high or low amounts of any or all lipids or lipoproteins in the blood. Dyslipidemia is a risk factor for the development of atherosclerotic cardiovascular diseases, which include coronary artery disease, cerebrovascular disease, and peripheral artery disease. Although dyslipidemia is a risk factor for cardiovascular disease, abnormal levels do not mean that lipid lowering agents need to be started. Other factors, such as comorbid conditions and lifestyle in addition to dyslipidemia, is considered in a cardiovascular risk assessment. In developed countries, most dyslipidemias are hyperlipidemias; that is, an elevation of lipids in the blood. This is often due to diet and lifestyle. Prolonged elevation of insulin resistance can also lead to dyslipidemia.
Atorvastatin is a statin medication used to prevent cardiovascular disease in those at high risk and to treat abnormal lipid levels. For the prevention of cardiovascular disease, statins are a first-line treatment. It is taken by mouth.
Hyperlipidemia is abnormally high levels of any or all lipids or lipoproteins in the blood. The term hyperlipidemia refers to the laboratory finding itself and is also used as an umbrella term covering any of various acquired or genetic disorders that result in that finding. Hyperlipidemia represents a subset of dyslipidemia and a superset of hypercholesterolemia. Hyperlipidemia is usually chronic and requires ongoing medication to control blood lipid levels.
Foam cells, also called lipid-laden macrophages, are a type of cell that contain cholesterol. These can form a plaque that can lead to atherosclerosis and trigger myocardial infarction and stroke.
The lipid hypothesis is a medical theory postulating a link between blood cholesterol levels and the occurrence of cardiovascular disease. A summary from 1976 described it as: "measures used to lower the plasma lipids in patients with hyperlipidemia will lead to reductions in new events of coronary heart disease". It states, more concisely, that "decreasing blood cholesterol [...] significantly reduces coronary heart disease".
Familial hypercholesterolemia (FH) is a genetic disorder characterized by high cholesterol levels, specifically very high levels of low-density lipoprotein cholesterol, in the blood and early cardiovascular diseases. The most common mutations diminish the number of functional LDL receptors in the liver or produce abnormal LDL receptors that never go to the cell surface to function properly. Since the underlying body biochemistry is slightly different in individuals with FH, their high cholesterol levels are less responsive to the kinds of cholesterol control methods which are usually more effective in people without FH. Nevertheless, treatment is usually effective.
Proprotein convertase subtilisin/kexin type 9 (PCSK9) is an enzyme encoded by the PCSK9 gene in humans on chromosome 1. It is the 9th member of the proprotein convertase family of proteins that activate other proteins. Similar genes (orthologs) are found across many species. As with many proteins, PCSK9 is inactive when first synthesized, because a section of peptide chains blocks their activity; proprotein convertases remove that section to activate the enzyme. The PCSK9 gene also contains one of 27 loci associated with increased risk of coronary artery disease.
A lipid profile or lipid panel is a panel of blood tests used to find abnormalities in blood lipid concentrations. The results of this test can identify certain genetic diseases and can determine approximate risks for cardiovascular disease, certain forms of pancreatitis, and other diseases.
Alirocumab, sold under the brand name Praluent, is a medication used as a second-line treatment for high cholesterol for adults whose cholesterol is not controlled by diet and statin treatment. It is a human monoclonal antibody that belongs to a novel class of anti-cholesterol drugs, known as PCSK9 inhibitors, and it was the first such agent to receive FDA approval. The FDA approval was contingent on the completion of further clinical trials to better determine efficacy and safety.
Remnant cholesterol, also known as remnant lipoprotein and triglyceride-rich lipoprotein cholesterol is an atherogenic lipoprotein composed primarily of very low-density lipoprotein (VLDL) and intermediate-density lipoprotein (IDL) with chylomicron remnants. Elevated remnant cholesterol is associated with increased risk of atherosclerotic cardiovascular disease and stroke.
Inclisiran, sold under the brand name Leqvio, is a medication used for the treatment of high low-density lipoprotein (LDL) cholesterol and for the treatment of people with atherosclerotic cardiovascular disease (ASCVD), ASCVD risk-equivalents, and heterozygous familial hypercholesterolemia (HeFH). It is a small interfering RNA (siRNA) that acts as an inhibitor of a proprotein convertase, specifically, inhibiting translation of the protein PCSK9.
Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides: Impact on Global Health Outcomes was a randomized control trial designed to assess the efficacy of niacin (extended-release) added to statin therapy in reducing cardiovascular events in patients with established atherosclerotic cardiovascular disease (ASCVD). These patients had well-controlled low-density lipoprotein (LDL) cholesterol but persistently low high-density lipoprotein (HDL) cholesterol and elevated triglycerides. 3,414 patients with established ASCVD were enrolled. The mean follow-up period was three years. The trial was stopped early due to a lack of efficacy and a trend towards an increase in the incidence of ischemic stroke.
{{cite journal}}: CS1 maint: DOI inactive as of November 2024 (link) Lipids: lipoprotein particle metabolism | ||
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| Lipoprotein particle classes and subclasses |
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| Apolipoproteins | ||
| Extracellular enzymes | ||
| Lipid transfer proteins | ||
| Cell surface receptors | ||
| ATP-binding cassette transporter | ||
