Lipoprotein-associated phospholipase A₂: role in atherosclerosis and utility as a cardiovascular biomarker

Abstract

Atherosclerosis and its clinical manifestations are widely prevalent throughout the world. Atherogenesis is highly complex and is modulated by numerous genetic and environmental risk factors. A large body of basic scientific and clinical research supports the conclusion that inflammation plays a significant role in atherogenesis along the entire continuum of its progression. Inflammation adversely impacts intravascular lipid handling and metabolism, resulting in the development of macrophage foam cells, fatty streaks and atheromatous plaque formation. Given the enormous human and economic cost of myocardial infarction, ischemic stroke, peripheral arterial disease and amputation, and premature death and disability, considerable effort is being committed to refining our ability to correctly identify patients at heightened risk for atherosclerotic vascular disease and acute cardiovascular events so that they can be treated earlier and more aggressively. Serum markers of inflammation have emerged as an important component of risk factor burden. Serum lipoprotein-associated phospholipase A₂ (Lp-PLA₂) potentiates intravascular inflammation and atherosclerosis. A variety of epidemiologic studies support the utility of Lp-PLA₂ measurements for estimating and further refining cardiovascular disease risk. Drug therapies to inhibit Lp-PLA₂ are in development and show considerable promise. In addition to substantially inhibiting Lp-PLA₂, darapladib reduces the progression of the necrotic core volume of coronary artery atheromatous plaque.

Keywords::

• atherosclerosis
• inflammation
• low-density lipoprotein cholesterol
• lysophosphatidylcholine
• macrophage
• oxidized fatty acid
• phospholipase
• phospholipid

Financial & competing interests disclosure

Peter P Toth is a speaker for diaDexus. Peter McCullough is a consultant for diaDexus. Michael Wegner and Kenneth Colley are medical directors for diaDexus. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.