Potential involvement of type II phospholipase A(2) in atherosclerosis

The presence of snpPLA2 in the arterial wall may be pro-atherogenic by two mechanisms: (1) it may induce local release of relatively high concentration of FFA and lyso-PC that may sustain inflammation and affect the functionality of cells at sites of LDL retention in the intima; and (2) snpPLA2 can modify LDL particles to a more atherogenic form, making them more susceptible to further oxidative and enzymatic modification. These mechanisms may be potentiated by the colocalization of snpPLA2 and LDL with sulfated GAGs. The positively charged snpPLA2 binds to negative charged PGs and GAGs. This could be a mechanism for retention and modulation of the activity of cell-secreted enzyme in cell membranes and extracellular matrices. However, the physiological functions(s) of snpPLA2 in arteries remains to be established. The participation of snpPLA2 in the generation of lipid derived factors, FFA and lyso-PC, involved in inflammation, cell proliferation and signal transduction, makes it an interesting subject for biochemical, genetic and pharmacological investigations.