The proteoglycan osteoglycin/mimecan is correlated with arteriogenesis.
Arteriogenesis or collateral growth is able to compensate for the stenosis of major arteries. Using differential display RT-PCR on growing and quiescent collateral arteries in a rabbit femoral artery ligation model, we cloned the rabbit full-length cDNA of osteoglycin/mimecan. Osteoglycin was present in the adventitia of collateral arteries as a glycosylated protein without keratan sulfate side chains, mainly produced by smooth muscle cells (SMCs) and perivascular fibroblasts. Northern blot, Western blot, and immunohistochemistry confirmed a collateral artery-specific downregulation of osteoglycin from 6 h to 3 weeks after the onset of arteriogenesis. Treatment of primary SMCs with the arteriogenic protein fibroblast growth factor-2 (FGF-2) resulted in a similar reduction of osteoglycin expression as observed in vivo. Application of the FGF-2 inhibitor polyanethole sulfonic acid (PAS) blocked the downregulation of osteoglycin and interfered with arteriogenesis. From our study we conclude that downregulation of osteoglycin is a fundamental requirement for proper arteriogenesis.
Kampmann
Andreas
A
Research Group Vascular Genomics, Kerckhoff Clinic, Bad Nauheim, Germany.
Fernández
Borja
B
Deindl
Elisabeth
E
Kubin
Thomas
T
Pipp
Frederic
F
Eitenmüller
Inka
I
Hoefer
Imo E
IE
Schaper
Wolfgang
W
Zimmermann
René
R
D000595:Amino Acid Sequence; D000818:Animals; D001158:Arteries / Q000254:growth & development; D001483:Base Sequence; D018076:DNA, Complementary / Q000737:chemistry; D015536:Down-Regulation; D005263:Femoral Artery / Q000254:growth & development*; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D023421:Models, Animal; D008969:Molecular Sequence Data; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D011509:Proteoglycans / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D020133:Reverse Transcriptase Polymerase Chain Reaction
D018076:DNA, Complementary; D011509:Proteoglycans; D012333:RNA, Messenger; D016222:Fibroblast Growth Factor 2