Phospholipase A(2)-modified LDL particles retain the generated hydrolytic products and are more atherogenic at acidic pH.
OBJECTIVE
Hydrolysis of LDL by phospholipase A(2) (PLA(2)) generates free fatty acids (FFAs) and lysophospholipids (lysoPCs). Binding of the PLA(2)-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 PLA(2)-induced LDL modification and its proatherogenic consequences.


RESULTS
LDL particles were avidly hydrolyzed by sPLA(2)-V at pH range 7.5-5.5. With decreasing pH, the ability of albumin to sequester the formed FFAs and lysoPCs from the sPLA(2)-V-modified LDL particles decreased, and, as a consequence, more of the hydrolytic products accumulated in the particles. At acidic pH, the sPLA(2)-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.


CONCLUSIONS
The present data show that the proatherogenic effects exerted by sPLA(2)-V-induced lipolysis of LDL are enhanced with decreasing pH and suggest that sPLA(2)-V is particularly atherogenic in advanced atherosclerotic lesions, in which local acidic conditions prevail.
Lähdesmäki
Katariina
K
Wihuri Research Institute, Kalliolinnantie 4, Helsinki, Finland.
Plihtari
Riia
R
Soininen
Pasi
P
Hurt-Camejo
Eva
E
Ala-Korpela
Mika
M
Oörni
Katariina
K
Kovanen
Petri T
PT
D001011:Aorta / Q000378:metabolism; D050197:Atherosclerosis / Q000201:enzymology*; D002478:Cells, Cultured; D005230:Fatty Acids, Nonesterified / Q000378:metabolism*; D005487:Foam Cells / Q000201:enzymology*; D054505:Group V Phospholipases A2 / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008066:Lipolysis; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008246:Lysophospholipids / Q000378:metabolism*; D011485:Protein Binding; D011509:Proteoglycans / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D012709:Serum Albumin / Q000378:metabolism; D013997:Time Factors
D005230:Fatty Acids, Nonesterified; D008077:Lipoproteins, LDL; D008246:Lysophospholipids; D011509:Proteoglycans; D011994:Recombinant Proteins; D012709:Serum Albumin; D054505:Group V Phospholipases A2