THE ROLE OF PROGENITOR CELLS IN ATHEROSCLEROSIS


Noel M. Caplice, M.D., Ph.D., University College Cork, Cork. Ireland

We previously showed that circulating cells with smooth muscle outgrowth potential exist in the peripheral circulation and that bone marrow derived precursor cells contribute to smooth muscle cells within murine and human atherosclerotic plaque. More recently we have defined a myeloid subpopulation of cells that undergo smooth muscle cell differentiation following signalling through the CX3CR1 chemokine receptor. We have shown in rodent models that competence of this CX3CR1 receptor is critical for myeloid smooth muscle cell transition within healing plaque in response to injury. Moreover receptor competence is essential in angiogenesis with respect to microvessel integrity and perivascular smooth muscle cell investment. This may have significant implications for drugs targeting both angiogenesis in general and CX3CR1 pathway in particular. More recently we have shown that this chemokine receptor pathway can be therapeutically antagonised with potent inhibition of intimal hyperplasia within stents and differential saving of endothelium. Together these data suggest new avenues for drug targeting in atherosclerosis and its treatment with interventional devices that presents both a therapeutic challenge in terms of unanticipated side effects and an opportunity in terms of selective cell targeting.