Abstract
Plaque calcification develops by the inflammation-dependent mechanisms involved in progression and regression of atherosclerosis. Macrophages can undergo two distinct polarization states, that is, pro-inflammatory M1 phenotype in progression and anti-inflammatory M2 phenotype in regression. In plaque progression, predominant M1 macrophages promote the initial calcium deposition within the necrotic core of the lesions, called as microcalcification, through not only vesicle-mediated mineralization as the result of apoptosis of macrophages and vascular smooth muscle cells (VSMCs), but also VSMC differentiation into early phase osteoblasts. On the other hand, in plaque regression M2 macrophages are engaged in the healing response to plaque inflammation. In association with the resolution of chronic inflammation, M2 macrophages may facilitate macroscopic calcium deposition, called as macrocalcification, through induction of osteoblastic differentiation and maturation of VSMCs. Oncostatin M, which has been shown to promote osteoblast differentiation in bone, may play a pivotal role in the development of plaque calcification. Clinically, two types of plaque calcification have distinct implications. Macrocalcification leads to plaque stability, while microcalcification is more likely to be associated with plaque rupture. Statin therapy, which reduces cardiovascular mortality, has been shown to exert its dual actions on plaque morphology, that is, regression of atheroma and increment of macroscopic calcium deposits. Statins may facilitate the healing process against plaque inflammation by enhancing M2 polarization of macrophages. Vascular calcification has pleiotropic properties as pro-inflammatory "microcalcification" and anti-inflammatory "macrocalcification". The molecular mechanisms of this process in relation with plaque progression as well as plaque regression should be intensively elucidated.