The pivotal role of lipoprotein lipase in atherosclerosis
Authors: J Mead
Journal: Cardiovascular Research (2002)

Introductionacids and 2-monoacylglycerols for tissue utilization [3,4].Due to the large size of its substrates, the physiological site Atherosclerosis, the underlying cause of heart attacks, of LPL action is at the luminal surface of blood vessels, to stroke and peripheral vascular disease, is responsible for which the enzyme is attached via highly charged heparan over 50% of all deaths in developed countries.The disease sulphate proteoglycans (HSPG) [3,4].Mature LPL is can generally be viewed as a form of chronic inflammation secreted to the vascular endothelium from the parenchymal that is induced and perturbed by lipid accumulation and cells of the adipose and muscle tissues, its major sites of involves a number of components, including the damaged synthesis, and a variety of other tissues which have also endothelium, monocytes / macrophages, T cells, smooth been implicated as lesser, but significant, sources of the muscle cells and a regulatory network of growth factors enzyme [3,4].Of these alternative sources, studies on LPL and cytokines (see Refs. [1,2] for reviews).The process is expressed by cell types found in the locus of the vascular believed to be triggered by damage to the arterial endo-wall, particularly by monocyte-derived macrophages, have thelial cells leading to dramatic changes in their properties identified additional, pathophysiological actions of the and increased expression of both chemokines and adhesion enzyme that promote foam cell formation and, ultimately, molecules [1,2].This causes an infiltration of both T atherosclerosis.In direct contrast to this, LPL produced by lymphocytes and monocytes to the site of damage.The adipose tissue and muscle has a protective effect with monocytes then differentiate into macrophages, internalise respect to atherosclerosis.As a result of these observations, lipoproteins, and transform into lipid-loaded foam cells to LPL has been identified as a potential therapeutic target form the fatty streak seen in early lesions [1,2].This and continues to be the subject of extensive scientific transformation of macrophages into foam cells represents a investigation.In this comprehensive and current review, critical initial event in the pathogenesis of atherosclerosis.the most recent evidence implicating LPL in both its pro-It is, therefore, not surprising that a major focus in and anti-atherogenic roles will be discussed.In addition, cardiovascular research has been devoted to understanding data regarding the regulation of the enzyme by factors the molecular basis of foam cell formation and has resulted involved in atherosclerosis will be covered.in the identification of a key, but complex, role of the enzyme lipoprotein lipase (LPL; EC 3.1.1.34)in the process.LPL is a central enzyme in overall lipid metabolism and 2 .Pro-atherogenic actions of LPL transport, being responsible for catalysing the hydrolysis of triglycerides transported in the bloodstream by chylomic-The importance of LPL in the atherosclerotic process rons and VLDL, thereby providing non-esterified fatty was first proposed in 1973 by Donald Zilversmit [5].He postulated that the action of LPL on circulating VLDL and chylomicrons would lead to high, localized concentrations Abbreviations: apoE, apolipoprotein E; HSPG, heparan sulphate proof cholesterol-rich remnants, which would subsequently be teoglycans; IFN-g, interferon-g; LPL, lipoprotein lipase; LRP, LDL taken up into the arterial wall and propagate lesion receptor-related protein; M-CSF, macrophage colony stimulating factor; TNF-a, tumour necrosis factor-a formation.Since this hypothesis was formulated, it has