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


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.
Division of Pathophysiological and Experimental Pathology, Department of Pathology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Fukuoka 812-8582, Japan.
Hiromitsu
H
Baba
Yoshikazu
Y
Yonemitsu
Toshiaki
T
Nakano
Mitsuho
M
Onimaru
Masanori
M
Miyazaki
Yasuhiro
Y
Ikeda
Shinji
S
Sumiyoshi
Yasuji
Y
Ueda
Mamoru
M
Hasegawa
Ichiro
I
Yoshino
Yoshihiko
Y
Maehara
Katsuo
K
Sueishi
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D003324:Coronary Artery Disease / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D003331:Coronary Vessels / Q000378:metabolism / Q000473:pathology; D003593:Cytoplasm / Q000378:metabolism; D005110:Extracellular Space / Q000378:metabolism; D005136:Eye Proteins / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D005487:Foam Cells / Q000473:pathology; D006801:Humans; D007231:Infant, Newborn; D008264:Macrophages / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D009414:Nerve Growth Factors / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D012160:Retina / Q000378:metabolism; D015843:Serpins / Q000235:genetics* / Q000378:metabolism*; D017539:Tunica Intima / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D000099174:Pigment Epithelium-Derived Factor
D005136:Eye Proteins; D009414:Nerve Growth Factors; D012333:RNA, Messenger; D015843:Serpins; D000099174:Pigment Epithelium-Derived Factor