Monocyte recruitment and neointimal hyperplasia in rabbits. Coupled inhibitory effects of heparin.
Among the many effects of heparin independent of its effects on coagulation are inhibition of vascular smooth muscle cell proliferation and regulation of leukocyte-blood vessel interactions. The potential link between these effects was examined in an animal model of vascular injury rich in inflammatory cells: the placement of endovascular metal stents in rabbit iliac arteries. Monocyte adhesion stimulated by early focal thrombus was maximal after 3 days, with infiltrating monocytes and intimal cell proliferation maximal after 7 days. Tissue monocyte number dictated cell proliferation at each time point (R2 = .92, P < .0001). Heparin reduced both early monocyte adhesion as well as monocyte infiltration within the neointima 7 and 14 days after stent placement. Reductions in adherent and tissue monocytes were commensurate with reductions in intimal cell proliferation and intimal thickening. At 14 days, heparin's inhibition of mononuclear cell adhesion was correlated with its suppression of intimal thickening (R2 = .82, P < .0001). Monocytes have been hypothesized to serve as markers, initiators, and promoters of arterial occlusive diseases. Heparin's ability to inhibit mononuclear cell adhesion and penetration and reduce neointimal size and cell proliferation after vascular injury may further implicate monocytes in the pathogenesis of neointimal hyperplasia after mechanical arterial injury.
Rogers
C
C
Department of Medicine, Harvard Medical School, Boston, Mass, USA. cdrogers@bics.bwh.harvard.edu
Welt
F G
FG
Karnovsky
M J
MJ
Edelman
E R
ER
D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects*; D002465:Cell Movement / Q000187:drug effects*; D006493:Heparin / Q000494:pharmacology*; D007083:Iliac Artery / Q000473:pathology*; D009000:Monocytes / Q000473:pathology*; D011817:Rabbits; D015607:Stents; D017539:Tunica Intima / Q000473:pathology*
D000925:Anticoagulants; D006493:Heparin