63 M2 MACROPHAGE POLARIZATION AS A CAUSE OF VASCULARFIBROSIS AND STIFFENING IN HYPERTENSION

Abstract

Background: Arterial stiffening is a hallmark of hypertension and contributes to elevated systolic blood pressure (SBP), increased cardiac afterload, poor coronary perfusion, and end-organ damage. Hypertension is also associated with accumulation of macrophages in the vascular wall. Macrophages can exist in different activation states including pro-inflammatory M1 and anti-inflammatory/pro-fibrotic M2 phenotypes. We hypothesized that accumulation of M2 macrophages in the vascular wall during hypertension is a major cause of arterial fibrosis and stiffening. Methods & results: Ang II infusion (0.7 mg/kg/d, 14 d) in mice was associated with marked increases in SBP (tail cuff) and vascular collagen deposition (picrosirius red staining), and a modest increase in aortic stiffening (stress-strain analysis). Flow cytometry revealed an increase in total macrophage (CD45+CD11b+F4/80+) numbers in aortas of Ang II- vs saline-treated mice (n = 16; P<0.05). Further analysis of these cells revealed an increase in the number of macrophages that were positive for the M2 surface antigen CD206, in Ang II-treated mice (n = 10; P<0.05). Finally, through real-time PCR we demonstrated increases in expression of M2 markers arginase-1 and Fc receptor-like S scavenger receptor (n = 4; P<0.05), but no changes in M1 markers inducible nitric oxide synthase, CXCL2 and tumour necrosis factor, in aortas from Ang II-treated mice. Conclusions: Hypertension in mice is associated with accumulation of M2 macrophage in the vascular wall. Future studies will determine whether inhibition of M2 macrophage trafficking and/or activation during hypertension is an effective strategy for reducing vascular fibrosis and stiffening, which likely underpins many of the clinical complications of the condition.