Abstract 19231: Chemotactic Properties of Perivascular Adipose Tissue in Angiotensin Ii Dependent Hypertension
Introduction. Recent studies show that immune system is involved in hypertension (HT). Angiotensin II (AngII) causes accumulation of T cells in perivascular adipose tissue (pvAT) but precise mechanisms of their infiltration remain unclear.
Hypothesis. RANTES and it’s receptors recruit T cells towards pvAT.
Methods. Expression of chemokine receptors on peripheral blood T cells and chemokine ligands in pvAT was studied by flow cytometry and quantitative RT-PCR respectively. Chemotaxis of T cells towards pvAT, vAT (epidydymal AT) or RANTES was studied in Boyden chambers.
Results. 14 day infusion of AngII (490mg/d/kg) was associated with significant increase in T cell content in pvAT with concomitant increase of RANTES mRNA expression (p<0.001). Expression of other CCR5 ligands MCP-1, MIP-1α and MIP-1β was significantly decreased. AngII significantly increased total content of T cells in pvAT expressing receptors for RANTES: CCR1 (27.9±4.6% vs.15.7±1%), CCR3 (17.1±1.4% vs.10.5±1.4%), CCR5 (23.6±0.9% vs.17±0.9%), while having no effect in vAT. T cells showed increased chemotaxis towards pvAT obtained from AngII infused mice when compared to sham animals (4.4±0.7 vs.0.17±0.17; p<0.01). Moreover pvAT attracted higher amount of T cells as compare to vAT (4.4±0.7% vs.0.8±0.1%; p<0.05); there was minimal migration toward subcutaneous fat. Moreover RANTES (10ng/ml) recruited T cells, but not B cells, from blood. Ang II infusion increased chemotaxis of blood derived T cells towards RANTES by 2-fold (p<0.01). However the most prominent chemotaxis potential was observed in pvAT isolated T cells from AngII treated mice (2.4±0.3% vs.0.8±0.2% in sham, p<0.01). CD4-CD8- T cells were characterized by the highest rate of migration towards RANTES. In contrast, migration capability of T cells resident in vAT was of minimal rate.
Conclusions. Ang II enhances T cell migration into pvAT but not vAT by increasing local RANTES expression. All known RANTES receptors are involved. And in particular CCR1 and CCR5 on CD3+CD4-CD8- cells.
- © 2012 by American Heart Association, Inc.