Cholesterol‐lowering Agents and their Use

Christopher J Packard, Glasgow Royal Infirmary, Glasgow, UK
Allan Gaw, Glasgow Royal Infirmary, Glasgow, UK
James Shepherd, Glasgow Royal Infirmary, Glasgow, UK

Published online: May 2003

DOI: 10.1038/npg.els.0002265

Abstract

Increased cholesterol concentration in the bloodstream is an important risk factor in coronary heart disease. Clinical trials have demonstrated the benefit of lipid‐lowering medication in preventing morbidity and death from coronary heart disease.

Keywords: dyslipidaemia; statin; fibrate; prevention; coronary

Figure 1.

Dietary cholesterol is absorped in the intestine and packaged into large (TG)‐rich chylomicrons. These apolipoprotein (apo) B48‐containing particles are released into the circulation in a wave following a fatty meal, and there are hydrolysed by the action of (LpL). This enzyme, present in skeletal muscle and adipose tissue, converts lipoprotein triglyceride to (FA). It is activated by apoCII on the surface of the particles and inhibited by apoCIII. ‘Remnants’ from LpL action are removed rapidly by the liver and the cholesterol is deposited in the organ ready for use in cellular processes or lipoprotein assembly. Synthesis from acetate is the other main source of body cholesterol. In the fasting state, very low‐density lipoprotein (VLDL) particles that contain apoB100 and triglyceride are released from the liver. These are converted to low‐density lipoprotein (LDL) by the action of LpL. LDL is then taken up in a regulated manner by receptors (R). When cells have sufficient cholesterol, the LDL receptor is downregulated and LDL accumulates in the bloodstream. It is eventually removed by (S‐R) on macrophages. In the artery wall this can lead to tissue cholesterol accumulation and atherosclerosis. Reverse cholesterol transport begins with the presentation of cholesterol at the cell surface and its transfer to apoAI (the major high‐density lipoprotein (HDL) protein) by the (ATP) binding cassette protein A1 (ABC‐A1). Once esterified in HDL, the cholesterol is either transported directly to the liver or exchanged via the action of (CETP) into VLDL and LDL.
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References

Barter PJ and Rye KA (2001) Cholesterol ester transfer protein, high density lipoprotein and arterial disease. Current Opinion in Lipidology 12: 377–382.

Brown MS and Goldstein JL (1997) The SREB pathway: regulation of cholesterol metabolism by proteolysis of a membrane‐bound transcription factor. Cell 89: 331–340.

Expert Panel (2001) Executive summary of the Third Report of the National Cholesterol Education Program (NCEP). Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Journal of the American Medical Association 285: 2486–2498.

Gervois P, Torra IP, Fruchart JC and Staels B (2000) Regulation of lipid and lipoprotein metabolism by PPAR activators. Clinical Chemistry and Laboratory Medicine 38: 3–11.

Grundy SM (1998) Statin trials and goals of cholesterol lowering therapy. Circulation 97: 1436–1439.

Illingworth DR (2000) Management of hypercholesterolemia. Medical Clinics of North America 84: 23–42.

Martin MJ, Hulley SB, Browner WS, Kuller LH and Wentworth D (1986) Serum cholesterol, blood pressure and mortality: implications from a cohort of 361 662 men. Lancet ii: 933–936.

Rosenson RS and Tangney CC (1998) Antiatherothrombotic properties of statins. Journal of the American Medical Association 279: 1642–1650.

Ross R (1999) Atherosclerosis: an inflammatory disease. New England Journal of Medicine 340: 115–126.

Stein EA, Lane M and Laskargweski P (1998) Comparison of statins in hypertriglyceridemia. American Journal of Cardiology 81: 66–69B.

Wood D, DeBacker G, Faergeman O et al. (1998) Prevention of coronary heart disease in clinical practice: recommendations of the Second Joint Task Force of European and other Societies on Coronary Prevention. Atherosclerosis 140: 199–270.

Further Reading

Davies MJ (1996) Stability and instability: two faces of coronary atherosclerosis. Circulation 94: 2013–2020.

Fruchart JC, Staels B and Duriez P (2001) PPARS, metabolic disease and atherosclerosis. Pharmacological Research 44: 345–352.

Goldstein JL and Brown MS (2001) Molecular medicine. The cholesterol quantet. Science 292: 1310–1312.

Packard CJ and Shepherd J (1997) Lipoprotein heterogeneity and apolipoprotein B metabolism. Arteriosclerosis, Thrombosis and Vascular Biology 17: 3542–3556.

Pearson TA (2000) Population benefits of cholesterol reduction: epidemiology, economics and ethics. American Journal of Cardiology 85: 20–23E.

Rubins HB, Robins SJ, Collins D et al. for the Veterans Affairs High‐Density Lipoprotein Cholesterol Intervention Trial Study Group (1999) Gemofibrozil for the secondary prevention of coronary heart disease in men with low levels of high‐density lipoprotein cholesterol. New England Journal of Medicine 341: 410–418.

Scandinavian Simvastatin Survival Study Group (1994) Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 344: 1383–1389.

Shepherd J, Cobbe SM, Isles CG et al. (1995) Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. New England Journal of Medicine 333: 1301–1307.

Thompson GR and Naumova RP (2000) Novel lipid regulating drugs. Expert Opinion in Investigational Drugs 9: 2619–2628.

Related Sub-Topics:

Biomolecular Interactions | Lipids: Structure, Function, Metabolism
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Article Title: Cholesterol‐lowering Agents and their Use
 
How to Cite close
Packard, Christopher J, Gaw, Allan, and Shepherd, James(May 2003) Cholesterol‐lowering Agents and their Use. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0002265]