Mechanisms of myeloid cell modulation of atherosclerosis

Concepts of the pathogenesis of atherosclerosis have evolved substantially through the decades. Viewing it as an inevitable degenerative process, Sir William Osler attributed atherosclerosis to the stress and strain of modern life at the dawn of the 20th century (1). Indeed, the pathogenesis of atherosclerosis had given rise to great controversy in the middle portion of the 19th century, particularly among German pathologists. Von Rokitansky postulated a role of incorporated thrombus into the artery wall as the primary event in atherosclerosis (2). Rudolf Virchow posited a role for proliferation of medial cells, now recognized as arterial smooth muscle cells (SMCs), in the pathogenesis of atherosclerosis (3). Virchow also recognized cell death as a component of atherogenesis and observed bone formation in atherosclerotic plaques. While von Rokitansky’s notion of the incorporation of thrombus lost popularity, the concept of atherosclerosis as a proliferative disorder of SMCs received considerable attention by pathologists and cell biologists in the latter part of the 20th century. Earl Benditt provided evidence for monotypic accumulation of SMCs in atherosclerotic plaques (4). Russell Ross focused on the role of platelet products, notably platelet-derived growth factor, as a causal stimulus for SMC growth in atherosclerotic plaques (5,6).