Abstract 455: M2 Macrophages Contribute to Vessel Fibrosis and Stiffening During Angiotensin II-Dependent Hypertension in Mice
Arterial fibrosis and stiffening are hallmarks of hypertension and contribute to elevated systolic blood pressure (BP), heart failure and end organ damage. Hypertension is also associated with accumulation of macrophages in the vascular wall; however, the phenotype of these cells (M1/M2) and their contribution to vascular fibrosis/stiffening remain to be established. Chronic angiotensin II-infusion in mice (0.7 mg/kg/d, 28 d) caused a marked increase in systolic BP (169±6 mmHg vs 118±3 mmHg in saline-infused mice). Flow cytometric analysis of aortic cell suspensions revealed that angiotensin II infusion also caused a 2-fold increase in F4/80+ macrophage numbers. Moreover, these cells were positive for the M2 marker, CD206. Quantitative PCR confirmed that aortic expression of CD206 and other M2 markers (arginase-1, Fc receptor-like S, scavenger receptor) were elevated in angiotensin II-infused mice, whereas levels of M1 markers (inducible nitric oxide synthase, CXCL2, tumour necrosis factor) were unchanged. Twice-weekly treatment of angiotensin II-infused mice with clodronate-encapsulated liposomes reduced numbers of circulating monocytes (i.e. macrophage precursors) by ~70%, whereas saline-containing liposomes had no effect. Clodronate treatment prevented M2 macrophage accumulation in the aorta, and also in the kidneys, and importantly reduced collagen deposition in these tissues. Clodronate treatment also improved arterial compliance and lowered BP by ~20 mmHg in angiotensin II-treated mice. In conclusion, M2 macrophages contribute to tissue fibrosis and aortic stiffening during angiotensin II-induced hypertension in mice. Thus, strategies that limit macrophage accumulation in the vessel wall and/or prevent their polarization towards an M2 phenotype may hold promise as future therapies for hypertension.
Author Disclosures: G.R. Drummond: None. J.P. Moore: None. K.L. Tuck: None. S. Sakkal: None. S.M. Krishnan: None. H. Diep: None. B.K. Kemp-Harper: None. K. Budzyn: None. S.D. Ricardo: None. T.J. Guzik: None. C.S. Samuel: None. C.G. Sobey: None.
- © 2014 by American Heart Association, Inc.