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

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• 作者：Katariina Lä ; hdesmä ; ki ; Riia Plihtari ; Pasi Soininen ; Eva Hurt-Camejo ; Mika Ala-Korpela ; Katariina Ö ; ö ; rni ; Petri T. Kovanen
• 关键词：LDL ; Phospholipase A₂ ; Proteoglycans ; Macrophage ; NMR
• 刊名：Atherosclerosis
• 出版年：2009
• 出版时间：December 2009
• 年：2009
• 卷：207
• 期：2
• 页码：352-359
• 全文大小：629 K

文摘

Objective

Hydrolysis 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.

Results

LDL 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.

Conclusions

The 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.