Cardiovascular diseases (CVDs) (such as heart attacks and strokes) are the leading cause of death and disability worldwide. During a heart attack or a stroke, blood flow to the heart or brain becomes limited causing cell death. This complex response (termed ‘thromboinflammation’) involves blood vessels, chemical mediators and immune cells (e.g. neutrophils and platelets). Thromboinflammation is also a severe complication of infection in CVD patients, although reasons why this is the case are still unknown.

 

Inflammation resolution restores homeostasis and involves specific endogenous mediators and protective pathways. While anti-inflammatory approaches have shown efficacy in CVD treatment, they often lead to immunosuppression and adverse events in patients. Novel immunotherapies that induce inflammation resolution are becoming attractive treatment options. We have identified that targeting the formyl peptide receptor-2 (Fpr2/ALX)-pathway, with the pro-resolution mediator Annexin A1 (AnxA1) affords protection in CVD pathologies. Specifically, we have shown that AnxA1 and its mimetic peptides (e.g. Ac2-26) exerts protection by altering neutrophil and platelet phenotypes from pro-pathogenic to regulatory in a murine stroke model and genetic AnxA1 deletion is associated with increased inflammation, but not spontaneous thrombosis or bleeding.

 

With British Heart Foundation funding, we are now using human cells and clinically relevant animal models of thrombosis to determine the effectiveness of Ac2-26 to reduce microvascular thrombosis with associated inflammation. These studies will provide invaluable information on the clinical condition of thromboinflammation in cardiovascular pathologies and aid in accelerating the screening and testing of newer and much needed therapies for CVD.