Secretory phospholipase A2 enzymes as pharmacological targets for treatment of disease

Phospholipase A(2) (PLA(2)) cleave phospholipids preferentially at the sn-2 position, liberating free fatty acids and lysophospholipids. They are classified into six main groups based on size, location, function, substrate specificity and calcium requirement. These classes include secretory PLA(2) (sPLA(2)), cytosolic (cPLA(2)), Ca2+-independent (iPLA(2)), platelet activating factor acetylhydrolases (PAF-AH), lysosomal PLA(2) (LyPLA(2)) and adipose specific PLA(2) (AdPLA(2)). It is hypothesized that PLA(2) can serve as pharmacological targets for the therapeutic treatment of several diseases, including cardiovascular diseases, atherosclerosis, immune disorders and cancer. Special emphasis has been placed on inhibitors of sPLA(2) isoforms as pharmacological moieties, mostly due to the fact that these enzymes are activated during inflammatory events and because their expression is increased in several diseases. This review focuses on understanding how sPLA(2) isoform expression is altered during disease progression and the possible therapeutic interventions to specifically target sPLA(2) isoforms, including new approaches using nano-particulate-based strategies. (C) 2014 Elsevier Inc. All rights reserved.