Abstract 5103: Perivascular Adipose Tissue in Angiotensin II Dependent Hypertension
Recent studies have suggested that perivascular adipose tissue (pvAT) is not just a mechanical scaffold for the vasculature but that it plays a critical role in vascular disease. The effects of mediators such as angiotensin II on perivascular adipose tissue however remain unknown. Accordingly, we examined the effects of chronic (14 day) angiotensin II (490ng/kg/min) infusion in mice on perivascular adipose tissue in comparison to effects on visceral (VAT) and subcutaneous (SAT) adipose tissue. Real time PCR and Western blotting showed that both AT1R and AT2R angiotensin II receptors were expressed in all studied compartments of AT but were greater in pvAT (485±90 vs. 45±18 in VAT and 3±0.7 in SAT U/ug RNA for AT1R mRNA; p<0.001). Angiotensin II infusion decreased epidydymal fat pad weight (413±45 mg vs 181±23mg; p<0.01) with concomitant increase of perivascular fat measured histologically (18±3 vs. 30±6 AU per aortic lumen; p<0.01). Interestingly, the cellularity of both pvAT and VAT increased (pvAT>>VAT) significantly but remained unchanged in SAT upon Angiotensin II infusion. Angiotensin II significantly altered adipocytokine expression in pvAT and VAT but not in SAT. Resistin levels increased in pvAT in response to angiotensin II, while leptin, visfatin and adiponectin decreased. The most significant changes were observed in inflammatory cytokines and chemokines. IL-6, TNF-a, IL-17A and were induced in pvAT to a greater degree than in VAT and were not changed by angiotensin II in SAT. Angiotensin II increased RANTES mRNA 6-fold in pvAT but not in VAT or SAT. Immunohistochemistry confirmed an increase in RANTES expression selectively in pvAT. These changes of cytokine and chemokine expression were accompanied by increased infiltration of pvAT with T lymphocytes expressing the RANTES receptor CCR5. These data indicate that angiotensin II affects adipocytokine and cytokine expression in adipose tissue and these effects are most pronounced in pvAT leading to T cell infiltration. These data indicate that the pvAT is a unique compartment of fat predisposed to angiotensin II-induced inflammation and a potential target for therapeutic intervention.