Interleukin-1β Is a Key Biomarker and Mediator of Inflammatory Vascular Calcification.

Atherosclerotic plaque calcification is a frequent and severe complication of atherosclerosis with significant clinical consequences. The causes of vascular calcification are multifactorial and include impaired phosphate metabolism, increased inflammation with consequent oxidative stress, alterations in systemic metabolic factors (hyperglycemia and hyperlipidemia), and alterations in tissue mechanical stress. Cytokines released by inflammatory cells induce smooth muscle cell (SMC) apoptosis or SMC transdifferentiation to osteochondrogenic phenotypes, both of which contribute to mineral deposition in the plaque. The calcium released in apoptotic bodies forms a nidus of microcalcification, prompting cycles of inflammation, thus making the plaque more susceptible to rupture. By contrast at later times in plaque progression, fusion of microcalcifications to form macrocalcification might actually convey protection against plaque rupture. Inflammatory cytokines can also stimulate the expression of osteogenic transcription factors by SMCs leading to phenotypic transition. Tumor necrosis factor-α (TNF-α), released primarily by macrophages, has been established as a key cytokine; in addition to promoting apoptosis and accumulation of apoptotic bodies, TNF-α is also an activator of osteogenic programming in SMCs via the BMP-2 (bone morphogenetic protein 2), Msx2 (msh homeobox 2), Wnt signaling cascade. Interleukin 1β (IL-1β) is another inflammatory cytokine reported to influence vascular calcification; however, the mechanisms involved are not completely clear and may be different from TNF-α.