Table 1.

Factors involved in dyslipidemia‐induced endothelial cell (EC) senescence

Factors	Functions	Mechanisms
Oxidized LDL	Increased SA‐β‐gal activity	GSK‐3β/catenin/p53 (Liu et al., 2015)
	Increased mitochondrial dysfunction	AMPK/p53/p21 (Zhang et al., 2017, 2018)
	Impaired proliferation; increased ROS and inflammation Increased ROS; impaired cell viability	NF‐κB, PI3K/AKT/eNOS (Bian et al., 2020) mTOR (Yao et al., 2017; Jiang et al., 2020)
	Increased SA‐β‐gal activity; upregulated p21 and p16	SIRT1/LKB1/AMPK (Zhang et al., 2019)
	Decreased proliferation; upregulated p21	SIRT1/Beclin‐1 (Shi et al., 2020)
Electronegative LDL	Increased DNA damage and nuclear γH2AX deposition	ROS/ATM/CHK2/p53 (Wang et al., 2018b)
Native LDL	Impaired proliferation; increased ROS	p53 and p16 (Oh et al., 2017; Yoon, Chay & Yang, 2019)
Palmitate	Impaired proliferation; increased ROS	PKR/JNK/SIRT1 (Y. Li et al., 2018a)
Palmitate and HG	Increased ROS; mitochondrial dysfunction	AKT (Liao et al., 2017)
	Increased ROS; upregulated p21 and p16	AMPK‐mediated autophagy (Wang et al., 2020)
LA	Impaired proliferation	JNK‐mediated autophagy (Lee et al., 2015)
Mediterranean diet	Decreased ROS, apoptosis and telomere shortening	Epigenetic alterations (Marin et al., 2012; Yubero‐Serrano et al., 2020)
EPA/DHA	Decreased ROS, inflammation and thrombosis	Angiotensin improvement (Yamagata, Suzuki & Tagami, 2016; Qureshi et al., 2020)
	Decreased DNA damage and ROS	Nrf2 (Sakai et al., 2017)
HDL containing glycated apoA‐1	Increased lysosomal enlargement, impaired anti‐senescence and insulin‐secretion activities	Structural modification (Park et al., 2016)

AKT, protein kinase B; AMPK, adenosine monophosphate‐activated protein kinase; apoA‐1, apolipoprotein A‐1; ATM, ataxia‐telangiectasia mutated; CHK2, checkpoint kinase 2; DHA, docosahexaenoic acid; eNOS, endothelial nitric oxide synthase; EPA, eicosapentaenoic acid; GSK‐3β, glycogen synthase kinase 3 beta; γH2AX, phosphorylated histone protein H2AX; HDL, high‐density lipoprotein; HG, high glucose; JNK, c‐Jun N‐terminal kinase; LA, linoleic acid; LDL, low‐density lipoproteins; LKB1, liver kinase B1; mTOR, mammalian target of rapamycin; NF‐κB, nuclear factor kappa‐B; Nrf2, nuclear factor erythroid 2‐related factor 2; PI3K, phosphatidylinositol 3‐kinase; PKR, protein kinase R; ROS, reactive oxygen species; SA‐β‐gal, senescence‐associated β‐galactosidase; SIRT1, silent information regulator 1.