Identification of an anti-inflammatory action of exosome release in P2Y 4 loss-mediated cardioprotection.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Introduction Exosomes are major actors in the progression of cardiovascular diseases and potential associated-treatments. We showed previously that inactivation of the mouse P2Y 4 nucleotide receptor induces a protection against myocardial infarction in the left anterior descending artery ligation model, characterized by smaller infarcts and reduced cardiac fibrosis and inflammation, compared to wild-type mice. This cardioprotection was associated with adiponectin and PD-L1 overexpression, regulatory leukocyte increase, and adipocyte beiging in the pericardial adipose tissue of P2Y 4 -null mice. We investigated here the contribution of exosome release in the cardioprotection observed in ischemic P2Y 4 -null mice. Methods and results Interestingly the reduction of cardiac fibrosis and T cell infiltration observed in P2Y 4 -null compared to wild-type ischemic heart was abolished after intraperitoneal injection of the exosome inhibitor GW4869 during myocardial infarction onset, as previously observed using an anti-PD-L1 blocking antibody. Additionally, GW4869 injection totally inhibited the increase in plasma PD-L1 level observed in P2Y 4 -null ischemic mice, as well as the higher T cell apoptosis in their pericardial adipose tissue, compared to wild-type mice. We observed increased expression of CDH13/T-cadherin, essential for adiponectin-driven exosome biogenesis, in P2Y 4 -null

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

Browse all related research

Filter the research library by this study's title keywords, author, or publication year.