Cytoplasmic expression and extracellular deposition of an antiangiogenic factor, pigment epithelium-derived factor, in human atherosclerotic plaques

Arterioscler Thromb Vasc Biol. 2005 Sep;25(9):1938-44. doi: 10.1161/01.ATV.0000175759.78338.1e. Epub 2005 Jun 30.

Abstract

Objective: To assess the expression and distribution of a neurotrophic/antiangiogenic factor, pigment epithelium-derived factor (PEDF), related to angiogenesis that is a possibly key event during atherogenesis in human atherosclerotic plaques.

Methods and results: Twenty fresh aortic samples were used for reverse-transcription polymerase chain reaction (RT-PCR), Western blot, and immunohistochemistry (IHC). In addition, 80 stocked paraffin blocks of coronary arteries from 40 autopsy cases were also used. IHC revealed divergent staining patterns for PEDF in both the aortas and the coronary arteries tested, ie, "cytoplasmic staining" or "extracellular deposition," were observed, respectively. In the areas showing cytoplasmic staining, double PEDF was expressed in a majority of the foamy macrophages and in some smooth muscle cells, and the PEDF-positive cell frequency was positively correlated with that of microvessels in a cell-rich area in the coronary arteries (P<0.0001). Inversely, extracellular deposition of PEDF was seen in acellular areas and was negatively correlated with the number of microvessels (P=0.0003).

Conclusions: These results suggest that PEDF may function as an antiangiogenic factor when it is deposited onto the extracellular matrix. Thus, PEDF may play a significant role in determining the balance of angiogenesis/ antiangiogenesis during atherogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Aorta / metabolism
  • Aorta / pathology
  • Coronary Artery Disease / immunology
  • Coronary Artery Disease / metabolism*
  • Coronary Artery Disease / pathology*
  • Coronary Vessels / metabolism
  • Coronary Vessels / pathology
  • Cytoplasm / metabolism
  • Extracellular Space / metabolism
  • Eye Proteins / genetics*
  • Eye Proteins / metabolism*
  • Female
  • Foam Cells / pathology
  • Humans
  • Infant, Newborn
  • Macrophages / pathology
  • Male
  • Middle Aged
  • Neovascularization, Pathologic / immunology
  • Neovascularization, Pathologic / metabolism
  • Neovascularization, Pathologic / pathology
  • Nerve Growth Factors / genetics*
  • Nerve Growth Factors / metabolism*
  • RNA, Messenger / analysis
  • Retina / metabolism
  • Serpins / genetics*
  • Serpins / metabolism*
  • Tunica Intima / immunology
  • Tunica Intima / metabolism
  • Tunica Intima / pathology

Substances

  • Eye Proteins
  • Nerve Growth Factors
  • RNA, Messenger
  • Serpins
  • pigment epithelium-derived factor