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Protein | Gene | Function | Calcification |
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IL-1β | IL1B (interleukin 1 beta) | Proinflammatory cytokine which promotes vascular calcification via NF-κB and Wnt signaling pathway | Intima/media |
IL-6 | IL6 (interleukin 6) | Proinflammatory cytokine which promotes vascular calcification through inflammation-induced oxidative stress. | Intima/media |
TNFα (tumor necrosis factor alpha) | TNF (tumor necrosis factor) | Inflammatory cytokine which promotes vascular calcification by increasing the expression of osteogenic genes. | Intima/media |
CRP | CRP (C-reactive protein) | Proinflammatory protein may contribute to vascular calcification through the raised expression of osteogenic factors such as Runx2 and TNAP. | Intima/media |
TNAP (tissue nonspecific alkaline phosphatase) | ALPL (gene encoding human TNAP) | Degrades inorganic pyrophosphate which makes VSMCs susceptible to calcification | Media |
Cbfa1/RUNX2 (RUNX family transcription factor 2) | RUNX2 (RUNX family transcription factor 2) | Transcription factor involved in chondrocyte and osteoblast differentiation | Media |
Osterix | SP7 (Sp7 transcription factor) | Controls the osteoblast differentiation and bone formation | Media |
BMP-2 (bone morphogenetic protein 2) | BMP2 (bone morphogenetic protein 2) | Osteogenic and osteoblast proliferation factor which upregulates the expression of Runx2 | Media |
Osteocalcin | BGLAP (bone gamma-carboxyglutamate protein) | Protein derived from osteoblasts, which stimulates the PI3K/Akt signaling pathway and upregulating the nuclear factor-kappa β (NF-кβ) | Media |
RANKL (receptor activator of nuclear factor kappa-B ligand)> | TNFS11 (TNF superfamily member) | Regulates osteoclast differentiation and activation | Media/intima |
RANK (receptor activator of nuclear factor kappa-B) | TNFRSF11A (TNF receptor superfamily member 11a) | Activates the transcription factor NF-κB for the generation and survival of osteoclasts | Media/intima |
NF-κB | NFKB (NF-kappa-B protein complex: NFKB1, NFKB2, RELA, RELB, and REL) | Transcription factor which promotes vascular calcification through the expression of MSX2 (which increases TNAP expression) and reduces the expression of ANKH through the expression of tritetraproline | Media/intima |
Wnt/β-catenin | WNT1/CTNNB1 (Wnt family member 1/catenin beta 1) | Through its canonical pathway promotes osteogenic gene expression via nuclear β-catenin dependent transcription | Media |
PTX3 | PTX3 (pentraxin 3) | It has been reported that PTX3 induces the expression of RANKL by human osteoblasts, thereby promoting osteoclastogenesis in vitro culture system | Media |
Inorganic pyrophosphate | — | Prevents the nucleation of amorphous calcium phosphate and inhibits hydroxyapatite crystallization | Media |
ANKH | ANKH (ankylosis, progressive homolog) | Inhibits mineralization by exporting inorganic pyrophosphate to the extracellular space to inhibit hydroxyapatite formation | Media |
Matrix gla protein | MGP (matrix gla protein) | Inhibits vascular mineralization by binding to calcium ions | Media |
Fetuin A | AHSG (alpha 2-HS glycoprotein) | Inhibitor of calcification by binding to calcium ions and forming calciprotein particles (CCPs) which prevent the precipitation of amorphous calcium phosphate particles | Media |
Osteoprotegerin | TNFRSF11B (TNF receptor superfamily member 11b) | Binds to RANKL as a decoy receptor resulting in down regulation of osteoclast differentiation, which decreases osteoclast activity | Media/intima |
DKK1 (Dickkopf Wnt signaling pathway inhibitor 1) | DKK1 (Dickkopf Wnt signaling pathway inhibitor 1) | Inhibitor of the canonical β-catenin-dependent Wnt pathway, it was shown to reduce the expression of Runx2 which is a canonical Wnt target | Media |
LRP5/6 (LDL receptor-related protein 5/6) | LRP5/6 (LDL receptor-related protein 5/6) | Wnt coreceptors that upon activation lead to stabilization of cytoplasm β-catenin, nuclear translocation, and target gene expression | Media |
Sclerostin | SOST (sclerostin) | Inhibitor of Wnt/β-catenin signaling, decreases bone formation by inhibiting osteoblastogenesis, in osteoclasts, and enhances bone resorption | Media |
Osteopontin | SPP1 (secreted phosphoprotein 1) | Inhibitor of mineralization and ectopic calcification linking the extracellular matrix with calcium | Media |
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