Table 1.

Vascular aging related epigentics targets.

Targets	Major findings	Effects	References
SIRT1	Decreases in VSMC of aged mice	Enhance vascular inflammation	(Chen et al., 2016)
	Deacetylate histone H4K16	Improves the function of endothelial cells	(Wan et al., 2014)
	Increase ECs KLF2 expressions	Vaso-protective	(Gracia-Sancho et al., 2010)
	Increased by energy limitation	Fight abdominal aortic aneurysm	(Liu et al., 2016)
	Activation by SIRT1 activators	Inhibit vascular remodeling, stiffness and calcification	(Takemura et al., 2011; Winnik et al., 2015; Fry et al., 2016; Badi et al., 2018)
SIRT2	Deacetylate p65Lys310	Regulates inflammmation via NF-κB-dependent gene expression	(Rothgiesser et al., 2019)
SIRT3	Missing will lead to the high acetylation and inactivation of SOD2	Leading to an imbalance of redox homeostasis in blood vessels	(Dikalova et al., 2017)
SIRT6	Protect telomere	Avoiding premature cell senescence caused by DNA damage	(Cardus et al., 2013)
HDAC3	Inhibit the activation of macrophages	Lacking HDAC3 will be easily activated by IL-4 and accelerate blood vessel’s inflammation	(Mullican et al., 2011)
HDAC4	Deacetylate FoxO3a	Regulates vascular inflammation via activation of autophagy	(Yang et al., 2018)
JMJD3	Deficiency of JMJD3 and Nox4 prohibits autophagic activation	Attenuates neointima and vascular remodelling following carotid injury	(Luo et al., 2018)
Fra-1	Directly binding and transcriptionally activating p21 and p16 signaling	Promoting vascular aging	(Yang et al., 2019)
GATA4	Directly binding to the the angiogenic factors VEGFA and VEGFC promoter and enhancing transcription.	Regulates Angiogenesis and Persistence of Inflammation	(Jia et al., 2018b)
MCP-1	Hypomethylation of the promoter region in atherosclerosis	Increases the expression of MCP-1, promotes the recruitment of inflammatory cells	(Liu et al., 2012)
eNOS	Hypermethylation of promoter region appears in pathological conditions	Inhibiting the expression of eNOS and NO production	(Chan et al., 2004)
p66Shc	Contains a large number of methylation modification sites	Modifying the methylation level to regulate the gene expression in order to control mitochondrial produce hydrogen peroxide	(Ventura et al., 2002; Cencioni et al., 2013)
miR-217	Combined with the (3’-UTR) of SIRT1 to inhibit the expression of SIRT1	Causing senescence and dysfunction of ECs	(Menghini et al., 2009)
miR-143/miR-145	miR-143 and miR-145 are activated in differentiated smooth muscle cells	Inhibits the proliferation of smooth muscle cells	(Cordes et al., 2009)
miR-210	Reduce the overproduction of ROS	Regulates oxidation stress	(Ma et al., 2018)
miR-135a/miR-714/miR-762/miR-712	Inhibit the outflow of calcium ions by disrupting Ca2+ efflux proteins NCX1, PMCA1, and NCKX4	Promote VSMC calcification	(Gui et al., 2012)
Long non-coding RNA H19	Decreased expressed along with aging in the adult endothelium	Inhibits STAT3 signaling pathway to regulate endothelial cell senescence	(Hofmann et al., 2019)
Long noncoding RNA MEG3	Impairing miR-128-dependent girdin down regulation	Prevents vascular endothelial cell senescence	(Lan et al., 2019)

SIRT, type III histone deacetylases (Sirtuin); VSMC, vascular smooth muscle cell; H4K16, histone4 Lysine16; KLF2, endothelial cells Kruppel-like factor 2. SOD2, superoxide dismutase 2; HDAC, histone deacetylase; FoxO3a, Forkhead boxO3;MCP-1, monocyte chemoattractant protein-1; P66Shc, member of Shc (src homology and collagen homology) family; 3’-UTR, 3’-untranslated region; eNOS, endothelial nitric oxide synthase; NO, nitric oxide; ROS, reactive oxygen species; JMJD3, histone demethylase; GATA4, a member of GATA zinc-finger transcription factor family; Fra-1, Fos-related antigen1; NF-κB, nuclear factor kappa-B; miR, micro RNA; NCX1, Na⁺-Ca²⁺ exchanger isoform 1; NCKX4, Na⁺/K^+/Ca²⁺-exchange protein 4; PMCA1, plasma membrane calcium ATPase 1; STAT3, signal transducers and activators of transcription.