Monocyte chemoattractant protein-1 or macrophage inflammatory protein-1alpha deficiency does not affect angiotensin II-induced intimal hyperplasia in carotid artery ligation model.
BACKGROUND
Angiotensin II (Ang II) promotes atherosclerotic vascular diseases, in which proinflammatory and proliferative effects play a major pathogenic role. Ang II up-regulates chemokines, such as monocyte chemoattractant protein (MCP)-1 and macrophage inflammatory protein (MIP)-1alpha, which are important pro-inflammatory factors mediating infiltration of inflammatory cells into atherosclerotic lesion. The aim of the present study was to determine whether the presence of MCP-1 or MIP-1alpha is essential in Ang II-induced intimal hyperplasia in the carotid artery ligation model.


METHODS
Six-month-old male C57BL/6-, MCP-1-, or MIP-1alpha-deficient mice underwent ligation of the common left carotid artery and were randomly assigned to receive either vehicle or Ang II (1.4 mg kg(-1) day(-1)) via a subcutaneously implanted osmotic infusion pump (model 2004, Alzet) for 4 weeks.


RESULTS
Ang II not only increased MCP-1 and MIP-1alpha production but also enhanced neo-intimal formation, media thickness, and adventitia development in the ligated carotid arteries in C57BL/6 mice. However, MCP-1 or MIP-1alpha deficiency failed to affect intimal hyperplasia in vascular remodeling.


CONCLUSIONS
These results indicate that MCP-1 or MIP-1alpha may not be essential in mediating the proliferative effects of Ang II, a major pathological changes in intimal hyperplasia in the carotid artery ligation model.
Zhang
Le-Ning
LN
Department of Pharmacology, Berlex Bioscience, Richmond, CA 94806, USA. le-ning_zhang@berlex.com
da Cunha
Valdeci
V
Martin-McNulty
Baby
B
Rutledge
John
J
Vergona
Ronald
R
Sullivan
Mark E
ME
Wang
Yi-Xin Jim
YX
D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D002339:Carotid Arteries / Q000378:metabolism* / Q000473:pathology; D020212:Carotid Artery Injuries / Q000378:metabolism / Q000473:pathology; D018932:Chemokine CCL2 / Q000378:metabolism*; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D006965:Hyperplasia; D007150:Immunohistochemistry; D008026:Ligation; D019402:Macrophage Inflammatory Proteins / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017539:Tunica Intima / Q000378:metabolism / Q000473:pathology*
C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D019402:Macrophage Inflammatory Proteins; D000804:Angiotensin II