Involvement of the chemokine CCL5/RANTES and its receptors in atherosclerosis and myocardial ischemia-reperfusion injury

Cardiovascular disease is the leading cause of morbidity and mortality in the adult population in industrialized countries. It is now well-established that immuno-inflammatory processes are involved in several cardiovascular diseases, such as atherosclerosis and myocardial infarction. Chemokines are known to trigger and direct leukocyte trafficking from the blood to inflamed tissues through the binding to their cell-surface receptors. Chemokines and there receptors are involved in multiple inflammatory diseases such as atherosclerosis, rheumatoid arthritis, multiple sclerosis or chronic obstructive pulmonary disease, as well as HIV infectious disease, making them particularly attractive therapeutic targets. In this thesis, we investigated the role of the chemokine CCL5/RANTES and its receptors in atherogenesis and myocardial reperfusion injury. Using both pharmacological and genetic approaches, we showed that inhibition of CCL5/RANTES and its receptor CCR5 could represent an attractive therapeutic strategy to decrease atherosclerosis progression and limit damages due to the reperfusion of ischemic myocardium, in mice.