Acidity and lipolysis by group V secreted phospholipase A(2) strongly increase the binding of apoB-100-containing lipoproteins to human aortic proteoglycans

Katariina Lahdesmaki, Katariina Öörni, Mervi Alanne-Kinnunen, Matti Jauhiainen, Eva Hurt-Camejo, Petri T. Kovanen

Research output: Contribution to journalArticleScientificpeer-review

Abstract

Local acidic areas characterize diffuse intimal thickening (DIT) and advanced atherosclerotic lesions. The role of acidity in the modification and extra- and intracellular accumulation of triglyceride-rich VLDL and IDL particles has not been studied before. Here, we examined the effects of acidic pH on the activity of recombinant human group V secreted phospholipase A(2) (sPLA(2)-V) toward small VLDL (sVLDL), IDL, and LDL, on the binding of these apoB-100-containing lipoproteins to human aortic proteoglycans, and on their uptake by human monocyte-derived macrophages. At acidic pH, the ability of sPLA(2)-V to lipolyze the apoB-100-containing lipoproteins was moderately, but significantly, increased while binding of the lipoproteins to proteoglycans increased >60-fold and sPLA(2)-V-modification further doubled the binding. Moreover, acidic pH more than doubled macrophage uptake of soluble complexes of sPLA(2)-V-LDL with aortic proteoglycans. Proteoglycan-affinity chromatography at pH 7.5 and 5.5 revealed that sVLDL, IDL, and LDL consisted of populations with different proteoglycan-binding affinities, and, surprisingly, the sVLDL fractions with the highest proteoglycan-affinity contained only low amounts of apolipoproteins E and C-III. Our results suggest that in atherosclerotic lesions with acidic extracellular pH, sPLA(2)-V is able to lipolyze sVLDL, IDL, and LDL, and increase their binding to proteoglycans. This is likely to provoke extracellular accumulation of lipids derived from these atherogenic lipoprotein particles and to increase the progression of the atherosclerotic lesions.
Original languageEnglish
JournalBiochimica and Biophysica Acta. Molecular and Cell Biology of Lipids
Volume1821
Issue number2
Pages (from-to)257-267
Number of pages11
ISSN1388-1981
DOIs
Publication statusPublished - Feb 2012
MoE publication typeA1 Journal article-refereed

Fields of Science

  • Acidic pH
  • Atherosclerosis
  • Macrophage
  • Triglyceride-rich lipoprotein
  • sPLA(2)-V
  • Aortic proteoglycan
  • LOW-DENSITY-LIPOPROTEIN
  • FOAM CELL-FORMATION
  • SPHINGOMYELINASE INDUCES AGGREGATION
  • RABBIT ATHEROSCLEROTIC PLAQUES
  • MONOCYTE-DERIVED MACROPHAGES
  • HUMAN ARTERIAL PROTEOGLYCANS
  • B-CONTAINING LIPOPROTEINS
  • VERY-LOW-DENSITY
  • FREE FATTY-ACIDS
  • APOLIPOPROTEIN-B
  • 3111 Biomedicine

Cite this

@article{21d4b2079f354aa3bee8ed69e4895411,
title = "Acidity and lipolysis by group V secreted phospholipase A(2) strongly increase the binding of apoB-100-containing lipoproteins to human aortic proteoglycans",
abstract = "Local acidic areas characterize diffuse intimal thickening (DIT) and advanced atherosclerotic lesions. The role of acidity in the modification and extra- and intracellular accumulation of triglyceride-rich VLDL and IDL particles has not been studied before. Here, we examined the effects of acidic pH on the activity of recombinant human group V secreted phospholipase A(2) (sPLA(2)-V) toward small VLDL (sVLDL), IDL, and LDL, on the binding of these apoB-100-containing lipoproteins to human aortic proteoglycans, and on their uptake by human monocyte-derived macrophages. At acidic pH, the ability of sPLA(2)-V to lipolyze the apoB-100-containing lipoproteins was moderately, but significantly, increased while binding of the lipoproteins to proteoglycans increased >60-fold and sPLA(2)-V-modification further doubled the binding. Moreover, acidic pH more than doubled macrophage uptake of soluble complexes of sPLA(2)-V-LDL with aortic proteoglycans. Proteoglycan-affinity chromatography at pH 7.5 and 5.5 revealed that sVLDL, IDL, and LDL consisted of populations with different proteoglycan-binding affinities, and, surprisingly, the sVLDL fractions with the highest proteoglycan-affinity contained only low amounts of apolipoproteins E and C-III. Our results suggest that in atherosclerotic lesions with acidic extracellular pH, sPLA(2)-V is able to lipolyze sVLDL, IDL, and LDL, and increase their binding to proteoglycans. This is likely to provoke extracellular accumulation of lipids derived from these atherogenic lipoprotein particles and to increase the progression of the atherosclerotic lesions.",
keywords = "Acidic pH, Atherosclerosis, Macrophage, Triglyceride-rich lipoprotein, sPLA(2)-V, Aortic proteoglycan, LOW-DENSITY-LIPOPROTEIN, FOAM CELL-FORMATION, SPHINGOMYELINASE INDUCES AGGREGATION, RABBIT ATHEROSCLEROTIC PLAQUES, MONOCYTE-DERIVED MACROPHAGES, HUMAN ARTERIAL PROTEOGLYCANS, B-CONTAINING LIPOPROTEINS, VERY-LOW-DENSITY, FREE FATTY-ACIDS, APOLIPOPROTEIN-B, 3111 Biomedicine",
author = "Katariina Lahdesmaki and Katariina {\"O}{\"o}rni and Mervi Alanne-Kinnunen and Matti Jauhiainen and Eva Hurt-Camejo and Kovanen, {Petri T.}",
year = "2012",
month = "2",
doi = "10.1016/j.bbalip.2011.10.014",
language = "English",
volume = "1821",
pages = "257--267",
journal = "Biochimica and Biophysica Acta. Molecular and Cell Biology of Lipids",
issn = "1388-1981",
publisher = "Elsevier Scientific Publ. Co",
number = "2",

}

Acidity and lipolysis by group V secreted phospholipase A(2) strongly increase the binding of apoB-100-containing lipoproteins to human aortic proteoglycans. / Lahdesmaki, Katariina; Öörni, Katariina; Alanne-Kinnunen, Mervi; Jauhiainen, Matti; Hurt-Camejo, Eva; Kovanen, Petri T.

In: Biochimica and Biophysica Acta. Molecular and Cell Biology of Lipids, Vol. 1821, No. 2, 02.2012, p. 257-267.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - Acidity and lipolysis by group V secreted phospholipase A(2) strongly increase the binding of apoB-100-containing lipoproteins to human aortic proteoglycans

AU - Lahdesmaki, Katariina

AU - Öörni, Katariina

AU - Alanne-Kinnunen, Mervi

AU - Jauhiainen, Matti

AU - Hurt-Camejo, Eva

AU - Kovanen, Petri T.

PY - 2012/2

Y1 - 2012/2

N2 - Local acidic areas characterize diffuse intimal thickening (DIT) and advanced atherosclerotic lesions. The role of acidity in the modification and extra- and intracellular accumulation of triglyceride-rich VLDL and IDL particles has not been studied before. Here, we examined the effects of acidic pH on the activity of recombinant human group V secreted phospholipase A(2) (sPLA(2)-V) toward small VLDL (sVLDL), IDL, and LDL, on the binding of these apoB-100-containing lipoproteins to human aortic proteoglycans, and on their uptake by human monocyte-derived macrophages. At acidic pH, the ability of sPLA(2)-V to lipolyze the apoB-100-containing lipoproteins was moderately, but significantly, increased while binding of the lipoproteins to proteoglycans increased >60-fold and sPLA(2)-V-modification further doubled the binding. Moreover, acidic pH more than doubled macrophage uptake of soluble complexes of sPLA(2)-V-LDL with aortic proteoglycans. Proteoglycan-affinity chromatography at pH 7.5 and 5.5 revealed that sVLDL, IDL, and LDL consisted of populations with different proteoglycan-binding affinities, and, surprisingly, the sVLDL fractions with the highest proteoglycan-affinity contained only low amounts of apolipoproteins E and C-III. Our results suggest that in atherosclerotic lesions with acidic extracellular pH, sPLA(2)-V is able to lipolyze sVLDL, IDL, and LDL, and increase their binding to proteoglycans. This is likely to provoke extracellular accumulation of lipids derived from these atherogenic lipoprotein particles and to increase the progression of the atherosclerotic lesions.

AB - Local acidic areas characterize diffuse intimal thickening (DIT) and advanced atherosclerotic lesions. The role of acidity in the modification and extra- and intracellular accumulation of triglyceride-rich VLDL and IDL particles has not been studied before. Here, we examined the effects of acidic pH on the activity of recombinant human group V secreted phospholipase A(2) (sPLA(2)-V) toward small VLDL (sVLDL), IDL, and LDL, on the binding of these apoB-100-containing lipoproteins to human aortic proteoglycans, and on their uptake by human monocyte-derived macrophages. At acidic pH, the ability of sPLA(2)-V to lipolyze the apoB-100-containing lipoproteins was moderately, but significantly, increased while binding of the lipoproteins to proteoglycans increased >60-fold and sPLA(2)-V-modification further doubled the binding. Moreover, acidic pH more than doubled macrophage uptake of soluble complexes of sPLA(2)-V-LDL with aortic proteoglycans. Proteoglycan-affinity chromatography at pH 7.5 and 5.5 revealed that sVLDL, IDL, and LDL consisted of populations with different proteoglycan-binding affinities, and, surprisingly, the sVLDL fractions with the highest proteoglycan-affinity contained only low amounts of apolipoproteins E and C-III. Our results suggest that in atherosclerotic lesions with acidic extracellular pH, sPLA(2)-V is able to lipolyze sVLDL, IDL, and LDL, and increase their binding to proteoglycans. This is likely to provoke extracellular accumulation of lipids derived from these atherogenic lipoprotein particles and to increase the progression of the atherosclerotic lesions.

KW - Acidic pH

KW - Atherosclerosis

KW - Macrophage

KW - Triglyceride-rich lipoprotein

KW - sPLA(2)-V

KW - Aortic proteoglycan

KW - LOW-DENSITY-LIPOPROTEIN

KW - FOAM CELL-FORMATION

KW - SPHINGOMYELINASE INDUCES AGGREGATION

KW - RABBIT ATHEROSCLEROTIC PLAQUES

KW - MONOCYTE-DERIVED MACROPHAGES

KW - HUMAN ARTERIAL PROTEOGLYCANS

KW - B-CONTAINING LIPOPROTEINS

KW - VERY-LOW-DENSITY

KW - FREE FATTY-ACIDS

KW - APOLIPOPROTEIN-B

KW - 3111 Biomedicine

U2 - 10.1016/j.bbalip.2011.10.014

DO - 10.1016/j.bbalip.2011.10.014

M3 - Article

VL - 1821

SP - 257

EP - 267

JO - Biochimica and Biophysica Acta. Molecular and Cell Biology of Lipids

JF - Biochimica and Biophysica Acta. Molecular and Cell Biology of Lipids

SN - 1388-1981

IS - 2

ER -