Phospholipase A2-modified LDL particles retain the generated hydrolytic products and are more atherogenic at acidic pH

ObjectiveHydrolysis of LDL by phospholipase A2 (PLA2) generates free fatty acids (FFAs) and lysophospholipids (lysoPCs). Binding of the PLA2-modified LDL to proteoglycans, and their uptake by macrophages are increased. Since the extracellular pH is locally decreased in advanced atherosclerotic plaques, we examined the effects of acidic pH on PLA2-induced LDL modification and its proatherogenic consequences.ResultsLDL particles were avidly hydrolyzed by sPLA2-V at pH range 7.5–5.5. With decreasing pH, the ability of albumin to sequester the formed FFAs and lysoPCs from the sPLA2-V-modified LDL particles decreased, and, as a consequence, more of the hydrolytic products accumulated in the particles. At acidic pH, the sPLA2-V-modified LDL particles had higher binding strength to human aortic proteoglycans, and their uptake by human monocyte-derived macrophages and ensuing foam cell formation were enhanced.ConclusionsThe present data show that the proatherogenic effects exerted by sPLA2-V-induced lipolysis of LDL are enhanced with decreasing pH and suggest that sPLA2-V is particularly atherogenic in advanced atherosclerotic lesions, in which local acidic conditions prevail.