Ultrastructure and molecular histology of rabbit hind-limb collateral artery growth (arteriogenesis).
Previous studies in the canine heart had shown that the growth of collateral arteries occurs via proliferative enlargement of pre-existing arteriolar connections (arteriogenesis). In the present study, we investigated the ultrastructure and molecular histology of growing and remodeling collateral arteries that develop after femoral artery occlusion in rabbits as a function of time from 2 h to 240 days after occlusion. Pre-existent arteriolar collaterals had a diameter of about 50 microm. They consisted of one to two layers of smooth muscle cells (SMCs) and were morphologically indistinguishable from normal arterioles. The stages of arteriogenesis consisted of arteriolar thinning, followed by transformation of SMCs from the contractile- into the proliferative- and synthetic phenotype. Endothelial cells (ECs) and SMCs proliferated, and SMCs migrated and formed a neo-intima. Intercellular adhesion molecule (ICAM-1) and vascular cell adhesion molecule (VCAM-1) showed early upregulation in ECs, which was accompanied by accumulation of blood-derived macrophages. Mitosis of ECs and SMCs started about 24 h after occlusion, whereas adhesion molecule expression and monocyte adhesion occurred as early as 12 h after occlusion, suggesting a role of monocytes in vascular cell proliferation. Treatment of rabbits with the pro-inflammatory cytokine MCP-1 increased monocyte adhesion and accelerated vascular remodeling. In vitro shear-stress experiments in cultured ECs revealed an increased phosphorylation of the focal contacts after 30 min and induction of ICAM-1 and VCAM-1 expression between 2 h and 6 h after shear onset, suggesting that shear stress may be the initiating event. We conclude that the process of arteriogenesis, which leads to the positive remodeling of an arteriole into an artery up to 12 times its original size, can be modified by modulators of inflammation.
Scholz
D
D
Department of Experimental Cardiology, Max-Planck-Institute, Bad Nauheim, Germany. d.scholz@kerckhoff.mpg.de
Ito
W
W
Fleming
I
I
Deindl
E
E
Sauer
A
A
Wiesnet
M
M
Busse
R
R
Schaper
J
J
Schaper
W
W
D000818:Animals; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D003097:Collateral Circulation; D004285:Dogs; D005263:Femoral Artery / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure*; D006614:Hindlimb / Q000098:blood supply*; D007150:Immunohistochemistry; D008854:Microscopy, Electron; D018919:Neovascularization, Physiologic; D011817:Rabbits
D015815:Cell Adhesion Molecules