Table 3.
Factors involved in dyslipidemia‐induced vascular smooth muscle cell (VSMC) senescence
| Factors | Functions | Mechanisms |
|---|---|---|
| Oxidized LDL | Increased SA‐β‐gal activity and ROS | p53/p21 and p16 (Zhu et al., 2019) |
| DNA damage | SIRT1/NBS1 (Gorenne et al., 2013) | |
| Impaired proliferation; increased p16 and p21 | mTOR/ULK1/ATG13 (Luo et al., 2017) | |
| Pro‐calcification |
CAG/TGF‐β (Yan et al., 2011) TLR4/NF‐κB (Song et al., 2017b) p38 MAPK (Liao et al., 2013) PI3K/AKT and ERK1/2 (Tang et al., 2015) FKN/CX3CR1 (Yang et al., 2020) |
|
| Lp (a) | Pro‐calcification | Increased ALP activity (Sun et al., 2002) |
| Palmitate | Increased inflammation; telomerase damage | p38 MAPK, JNK and ERK1/2 (Grootaert et al., 2021) |
| Palmitate | Pro‐calcification |
ROS‐dependent ERK1/2 (Brodeur et al., 2013) TGF‐β, BMP‐2, PKC, NF‐κB (Son et al., 2020) |
| EPA | Anti‐calcification | NOX (Nakamura et al., 2017) |
| Wnt (Saito et al., 2017) |
AKT, protein kinase B; ALP, alkaline phosphatase; ATG13, autophagy‐related protein 13; BMP‐2, bone morphogenetic protein 2; CAG, glycosaminoglycan; CX3CR1, C‐X3‐C motif chemokine receptor 1; EPA, eicosapentaenoic acid; ERK1/2, extracellular regulated protein kinase 1/2; FKN, Fractalkine; JNK, c‐Jun N‐terminal kinase; LDL, low‐density lipoprotein; Lp(a), lipoprotein(a); MAPK, mitogen‐activated protein kinase; mTOR, mammalian target of rapamycin; NBS1, Nijmegen Breakage Syndrome‐1; NF‐κB, nuclear factor kappa‐B; NOX, NADPH oxidase; PI3K, phosphatidylinositol 3‐kinase; PKC, protein kinase C; ROS, reactive oxygen species; SA‐β‐gal, senescence‐associated β‐galactosidase; SIRT1, silent information regulator 1; TGF‐β, transforming growth factor β; TLR4, toll‐like receptor 4; ULK1, Unc‐51 like autophagy activating kinase 1; Wnt, wingless.