Clinical & Experimental Cardiology
Open Access
ISSN: 2155-9880
+44 1300 500008
ISSN: 2155-9880
+44 1300 500008
Mizanur Rahman, Johnny Steuer, Peter Gillgren, Assim Hayderi, Anquan Liu and Johan Frostegard
Karolinska Institute, Sweden
Scientific Tracks Abstracts: J Clin Exp Cardiolog
Background: Atherosclerosis is characterized by presence of activated immune cells including dendritic cells (DCs) and T cells; dead cells and oxidized low-density lipoprotein (OxLDL). Role of heat shock protein 60 (HSP60) has been implicated in atherosclerosis. Annexin A5 (ANXA5) has atheroprotective properties. Methods & Results: Human DCs differentiated from peripheral blood monocytes of atherosclerotic patients, were treated with human HSP60 or HSP90. Autologous T cells from atherosclerotic plaques were co-cultured with these pre-treated DCs. DCs and T cell activation was determined by FACScan, gene-activation and cytokine production. HSP60-induced T cell activation was MHC class II-dependent. T cells exposed to HSP60-treated DCs produced pro-inflammatory Th1 type cytokines. DC-T cells from patients who were not treated with lipid lowering drugs secreted more pro-inflammatory cytokine in compare to DC-T cells from lipid lowering drug treated patients secreted more pro-inflammatory cytokine in response to HSP60. HSP90 promoted DCs maturation but did not induce T cell activation. ANXA5 inhibited pro-inflammatory effect of HSP60. Further, ANXA5 inhibited oxLDL-induced HSP-activation of DCs and HSP-production from DCs of healthy donors. Conclusions: HSP60 induces DCs-activation and induce MHC-II dependent pro-inflammatory T cell activation in atherosclerotic plaques. HSP60 could thus be an important T cell antigen in plaques, and mediate oxLDLs inflammatory effect, promoting plaque rupture and clinical manifestations of CVD. Anti-inflammatory effect of ANXA5 suggests a potential therapeutic role in cardiovascular disease.