Abnormal monocyte recruitment and collateral artery formation in monocyte chemoattractant protein-1 deficient mice.
Monocyte chemoattractant protein 1 (MCP-1) has been shown to be effective for the stimulation of collateral artery formation in small and large animal models. The availability of a genetic knockout mouse enables evaluation of the importance of the role of MCP-1 in the natural course of collateral artery growth. In a total of 21 MCP-1 -/- as well as 13 of the appropriate genetic background controls ([129Sv/J X C57BI/6J]F1), a femoral artery ligation was performed. Subsequently, a polyethylene catheter, connected to an osmotic minipump, was inserted retrogradely into the occluded femoral artery with the tip pointing upstream. Using this technique, PBS (MCP-1 -/-: n = 13 and C57BI/6J: n = 13) or MCP-1 (JE; MCP-1 -/-: n = 8) was delivered intra-arterially. Seven days after ligation, determination of hind limb flow was assessed by controlled tissue perfusion using differently labeled fluorescent microspheres. MCP-1 -/- mice exhibited a reduction of hind limb flow of 32.9 +/- 9.2% of the unligated hind limb, compared with 55.4 +/- 6.8% in C57BI/6J mice (p<0.01). MCP-1 -/- mice that underwent a subsequent 'rescue' treatment with MCP-1 showed a restoration of flow to a level of 47.4 +/- 9.8% (p = NS compared with PBS-treated C57BI/6J). Specific immunohistochemical staining for monocytes (MOMA-2: MCP-1 -/-, n = 5 and C57BI/6J, n = 5) showed a reduced number of monocytes around developing collateral arteries in the MCP-1 -/- mice. In conclusion, our data show that the absence of MCP-1 causes a strong reduction in flow restoration after femoral artery occlusion, coinciding with a reduced monocyte attraction, emphasizing the central role of this chemokine in the multifactorial process of collateral artery formation.
Voskuil
Michiel
M
Department of Cardiology, Academic Medical Center, Amsterdam, The Netherlands.
Hoefer
Imo E
IE
van Royen
Niels
N
Hua
Jing
J
de Graaf
Stijn
S
Bode
Christoph
C
Buschmann
Ivo R
IR
Piek
Jan J
JJ
D000818:Animals; D018932:Chemokine CCL2 / Q000172:deficiency*; D003097:Collateral Circulation; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism / Q000503:physiopathology; D005121:Extremities / Q000098:blood supply* / Q000601:surgery; D005260:Female; D005263:Femoral Artery / Q000166:cytology / Q000378:metabolism / Q000503:physiopathology; D007150:Immunohistochemistry; D008026:Ligation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000378:metabolism* / Q000473:pathology*; D010477:Perfusion; D012039:Regional Blood Flow
D018932:Chemokine CCL2