Cardiovascular disease remains the leading cause of morbidity and mortality worldwide, and atherosclerosis is firmly established as the principal underlying cause. Some of the earliest insights into atherosclerosis were provided in the mid-nineteenth century by Rudolf Virchow, who postulated that atherosclerosis is an active process that occurs in response to vessel injury and that inflammation has a primary role. Notably, although many aspects of Virchow’s hypothesis are consistent with what has been accepted today, the importance of his ideas would not begin to be appreciated for many years to come, as they were overshadowed by the prevailing view of atherosclerosis as merely a passive disorder of lipid storage.

Starting in the 1970s, a number of alternative lines of thought began to emerge, the most prominent of which implicated aberrant smooth muscle cell proliferation as the key event in the genesis of atherosclerotic lesions. Crucially, however, this hypothesis neglected to mention a role for immune cells and inflammation in atherosclerosis. Indeed, more than 100 years after Virchow’s remarks, observations of leukocytes in atherosclerotic vessels were only sporadically documented and the presence of these cells was generally considered to be an incidental by-product of disease.