Role of lipoprotein-associated phospholipase A2 in atherosclerosis and its potential as a therapeutic target

  • Macphee C
  • Nelson J
  • Zalewski A
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Abstract

Despite substantial progress in preventing adverse cardiovascular events with current therapeutic strategies, there remains an extensive residual risk of clinical events, particularly in high-risk patients. Because of the evidence implicating inflammation in the pathogenesis of atherosclerosis, identifying and targeting inflammatory pathways could help further reduce cardiovascular risk. There has been controversy regarding the role of lipoprotein-associated phospholipase A2 (Lp-PLA2) in atherosclerosis, partly because of the lack of simple animal models with a human-like pattern of Lp-PLA2 lipoprotein distribution. However, accumulating evidence from pathology, biology and epidemiology studies favors a pro-atherogenic rather than an atheroprotective role for the enzyme. In particular, Lp-PLA2 might play an important role in plaque vulnerability. As a result, additional studies are warranted to determine whether Lp-PLA2 inhibition improves plaque stability and ultimately clinical outcomes for high-risk patients. (copyright) 2006 Elsevier Ltd. All rights reserved

Author-supplied keywords

  • United States
  • alanine
  • animal
  • animal model
  • antiinflammatory activity
  • apolipoprotein B
  • atherosclerosis
  • cardiovascular disease
  • cardiovascular risk
  • clinical trial
  • drug potency
  • drug targeting
  • enzyme
  • enzyme inhibition
  • gene mutation
  • genetic polymorphism
  • genetic variability
  • heart infarction
  • heart protection
  • high density lipoprotein cholesterol
  • high risk patient
  • histopathology
  • human
  • inflammation
  • ischemic heart disease
  • lipoprotein
  • lipoprotein associated phospholipase A2
  • lipoprotein-associated phospholipase A2
  • low density lipoprotein cholesterol
  • lysophosphatidylcholine
  • molecular biology
  • nonhuman
  • outcome assessment
  • pathogenesis
  • pathology
  • phenylalanine
  • phospholipase
  • phospholipase A2
  • phospholipase A2 inhibitor
  • placebo
  • priority journal
  • protein binding
  • protein expression
  • protein function
  • protein localization
  • review
  • risk
  • risk reduction
  • signal transduction
  • thrombocyte activating factor
  • thrombosis
  • upregulation
  • valine

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  • PMID: 16495153

Authors

  • C H Macphee

  • J Nelson

  • A Zalewski

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