Macrophage death and the role of apoptosis in human atherosclerosis

The arterial disease atherosclerosis is responsible for severe morbidity an d is the most common cause of death in the Western population. The complete pathogenesis of the disease is unknown, but multiple risk factors have bee n identified that correlate with the development of its complications such as heart attack and stroke. Evidence suggests that atherosclerosis is an in flammatory disease and the major cell types involved are smooth muscle cell s, macrophages, and T lymphocytes. In this paper, we review the function of macrophages in the context of atherosclerosis and we also discuss the role and significance of macrophage death, including apoptosis. There is much e vidence, certainly in vitro, suggesting that low-density lipoprotein become s atherogenic when it undergoes cell-mediated oxidation within the artery w all. Besides inducing apoptosis in vitro, oxidized low-density lipoprotein may also cause extensive DNA damage in intimal cells, which might presage a poptosis. We review the results of experimental and clinical studies, which may indicate how the complications of atherosclerosis could be prevented b y using different therapeutical strategies including bone marrow transplant ation and gene therapy.