TABLE 1.

Inducing factors and the mechanism of vascular calcification.

Inducing factors	Mechanism	References
Calciprotein particles	Phosphate/calcium homeostasis disorders and changes in hormone levels (high FGF23, low vitamin D activity, and high parathyroid hormone)	Kuro, (2021)
Oxyphospholipids and their mediators	Oxyphospholipids in macrophages promote the assembly of inflammatory bodies and the production of cytokines with calcification-promoting properties. Macrophages promote and/or enhance plaque mineralization by generating extracellular vesicles	Chignon et al. (2021)
Platelet	Platelets involved in thrombosis release various bioactive molecules, some of which have calcification-promoting properties. Signal crosstalk between platelets and vascular/valve cells can promote ectopic mineralization	Schurgers et al. (2018)
Aging	Aging causes mitochondrial dysfunction and increased ROS production, activates inflammation, increases oxidative stress, upregulates BMPs and enhances the expression of the osteogenic transcription factor Runx2, which in turn promotes vascular calcification	Kwon et al. (2017)
Inflammation	By releasing proinflammatory cytokines, endothelial cells are induced to transform into mesenchymal cells, and vascular smooth muscle cells are reversely differentiated into osteoblasts, thereby promoting vascular calcification	Sanchez-Duffhues et al. (2019)
Diabetes	Hyperglycemia and an imbalance in mineral ion homeostasis lead to endothelial cell injury. The medial mucosal layer responds by triggering the repair response. CVCs perceive extracellular signals, upregulate osteogenic factors, downregulate sirtuin-1, and activate Wnt signaling, resulting in CVC differentiation into osteogenic cells and promoting vascular calcification	Bartoli-Leonard et al. (2018)
CKD	A decrease in fetal globulin A and pyrophosphate levels, increase in serum phosphate levels (hyperphosphatemia), hyperparathyroidism, and PTH and FGF23 deficiency could lead to calcium and phosphate imbalance and promote vascular calcification	Chen et al. (2020)
Hypertension	Blood pressure fluctuation changes the production of ATP, increases ROS, and disturbs the mitochondrial network in VSMCs, leading to mitochondrial dysfunction and eventually VC.	Bartolak-Suki and Suki, (2020)
Dyslipidemia	Polarization of induced proinflammatory (M1) function in the monocyte/macrophage system leads to an increased release of proinflammatory cytokines (e.g., IL-6, IL-1β, and TNF-α) and the production of reactive oxygen species, which in turn induce the calcification of VSMCs and ECs	Torres-Castro et al. (2016)
High phosphate	High phosphate levels can directly promote VSMC calcification, leading to VSMCs transforming from the contractile to osteochondral phenotype	Bai et al. (2021)
Klotho deficiency	Klotho deficiency leads to the upregulation of BMP2, BMP4, and Runx2 expression and promotes BMP2/VitD3-induced osteogenic transdifferentiation of VSMCs, leading to vascular calcification	Lin and Sun, (2021)