Abstract 11067: The Anti-Inflammatory Mechanism of Prostaglandin E2 Receptor 4 Activation in Rat Experimental Autoimmune Myocarditis
Background: Prostaglandins (PG) and their specific receptors for E type PG (EP) play an important role in inflammatory diseases. Although myocarditis results in inflammation of the heart, the role of PG and EP in that pathophysiology is still controversial.
Hypothesis: We assessed the hypothesis that PG and EP activation could attenuate acute myocarditis.
Methods and Results: To clarify the role of PG and EP on the progression of myocarditis, we used an experimental autoimmune myocarditis (EAM) model. A selective agonist of EP4 (EP4RAG) was administered into both early (day 0 to 21) and late (day 14 to 21) treated groups. The rats were killed on day 21. The reduction of pericardial effusion together with the improvement in cardiac function was detected in the EP4RAG treated groups in comparison to the untreated group. The infiltration area ratio in the early treated (16.6±4.6%) group was lower than those in the untreated group (32.1±3.5%) (p<0.05). The fibrosis area ratios in the early treated (19.2±6.3%) and the late treated groups (24.4±5.1%) were lower than those in the untreated group (37.4±2.6%), respectively (p<0.05). Moreover, we found that EP4RAG decreased T cell proliferation and MCP-1 production in response to the stimulation with porcine myosin.
Conclusions: A selective EP4 agonist inactivates T cells which turns out to moderate the progression of EAM. Therefore, EP4 can be an effective target for myocarditis treatment.
- © 2010 by American Heart Association, Inc.