OBJECTIVE: The CCR2 receptor plays a crucial role in monocyte recruitment and has been implicated as a contributing factor to atherosclerosis. CCR2 receptor deletion leads to significant inhibition of lesion development. Our objective was to determine if CCR2 receptor blockade with a small molecule would have a beneficial effect of decreasing established lesions. METHODS AND RESULTS: We demonstrated that CCR2 blockade had no significant effect on advanced lesions or the progression of fatty streaks. CCR2 blockade in mice resulted in elevations in plasma CCL2 levels and a significant reduction in the plasma Ly-6C(hi) subpopulations of monocytes expressing the CCR2 receptor. Neither CCL2 elevation nor margination of the Ly-6C(hi) population was observed in CCR2(-/-) mice. CONCLUSIONS: CCR2 receptor blockade with a small molecule antagonist at dose levels showing efficacy in several inflammatory models did not show a beneficial effect in murine models of atherosclerosis. Elevations in CCL2 and margination of Ly-6C(hi) cells demonstrate that the role of CCR2 in controlling monocyte levels goes beyond the control of monocyte emigration. Copyright 2009. Published by Elsevier Ireland Ltd.
OBJECTIVE: The CCR2 receptor plays a crucial role in monocyte recruitment and has been implicated as a contributing factor to atherosclerosis. CCR2 receptor deletion leads to significant inhibition of lesion development. Our objective was to determine if CCR2 receptor blockade with a small molecule would have a beneficial effect of decreasing established lesions. METHODS AND RESULTS: We demonstrated that CCR2 blockade had no significant effect on advanced lesions or the progression of fatty streaks. CCR2 blockade in mice resulted in elevations in plasma CCL2 levels and a significant reduction in the plasma Ly-6C(hi) subpopulations of monocytes expressing the CCR2 receptor. Neither CCL2 elevation nor margination of the Ly-6C(hi) population was observed in CCR2(-/-) mice. CONCLUSIONS:CCR2 receptor blockade with a small molecule antagonist at dose levels showing efficacy in several inflammatory models did not show a beneficial effect in murine models of atherosclerosis. Elevations in CCL2 and margination of Ly-6C(hi) cells demonstrate that the role of CCR2 in controlling monocyte levels goes beyond the control of monocyte emigration. Copyright 2009. Published by Elsevier Ireland Ltd.
Authors: Anne M Hüsing; Vera C Wulfmeyer; Svenja Gaedcke; Susanne V Fleig; Song Rong; David DeLuca; Hermann Haller; Roland Schmitt; Sibylle von Vietinghoff Journal: J Am Soc Nephrol Date: 2022-05-10 Impact factor: 14.978
Authors: Timothy Sullivan; Zhenhua Miao; Daniel J Dairaghi; Antoni Krasinski; Yu Wang; Bin N Zhao; Trageen Baumgart; Linda S Ertl; Andrew Pennell; Lisa Seitz; Jay Powers; Ruiping Zhao; Solomon Ungashe; Zheng Wei; Landin Boring; Chia-Lin Tsou; Israel Charo; Robert D Berahovich; Thomas J Schall; Juan C Jaen Journal: Am J Physiol Renal Physiol Date: 2013-08-28
Authors: Bin N Zhao; James J Campbell; Catherina L Salanga; Linda S Ertl; Yu Wang; Simon Yau; Ton Dang; Yibin Zeng; Jeffrey P McMahon; Antoni Krasinski; Penglie Zhang; Irina Kufareva; Tracy M Handel; Israel F Charo; Rajinder Singh; Thomas J Schall Journal: J Immunol Date: 2019-11-01 Impact factor: 5.422