Lysosomal enzymes are released from cultured human macrophages, hydrolyze LDL in vitro, and are present extracellularly in human atherosclerotic lesions

Jukka K. Hakala, Riina Oksjoki, Petri Laine, Hong Du, Gregory A. Grabowski, Petri T. Kovanen, Markku O. Pentikäinen

Research output: Contribution to journalArticle

90 Scopus citations

Abstract

Objective - Human atherosclerotic lesions have been shown to contain lipid droplets and vesicles resembling those of in vitro enzymatically modified LDL. However, little is known about the hydrolytic enzymes in the arterial intima that induce fusion of LDL particles and so produce lipid droplets or that induce foam cell formation. Methods and Results - Human coronary atherosclerotic lesions obtained at surgery and at autopsy were stained for lysosomal acid lipase and cathepsin D. The extracellular areas of macrophage-rich intimal regions of the atherosclerotic lesions stained positively for both cathepsin D and lysosomal acid lipase, whereas normal arteries were negative. When monocyte-derived macrophages were incubated with opsonized zymosan to stimulate the release of lysosomal enzymes from the cells and LDL was incubated with the macrophage-conditioned media, the apolipoprotein B-100, cholesteryl esters, and triacylglycerols of LDL were hydrolyzed. These hydrolytic modifications rendered the LDL particles unstable and induced their fusion. Cultured macrophages and smooth muscle cells took up the hydrolase-modified LDL particles avidly and were transformed into foam cells. Conclusions - Our in vivo and in vitro results suggest that lysosomal enzymes released from macrophages may induce hydrolytic modification of LDL and foam cell formation in the human arterial intima.

Original languageEnglish (US)
Pages (from-to)1430-1436
Number of pages7
JournalArteriosclerosis, thrombosis, and vascular biology
Volume23
Issue number8
DOIs
StatePublished - Aug 1 2003
Externally publishedYes

Keywords

  • Atherosclerosis
  • LDL
  • Lysosomal enzymes
  • Macrophage

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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