Table 2.

Senescent cardiovascular system contributes to cardiovascular disease

Senescent cell types	Features of cellular senescence	Cardiovascular disease or dysfunction
Endothelial cells	ICAM-1↑, DPP4↑ (Kim et al., 2017), eNOS↓ (Minamino et al., 2002), TAF↑ (Roos et al., 2016), PAI-1↑ (Comi et al., 1995; Xu et al., 2000), TSP1↑ (Meijles et al., 2017), telomere attrition (Cafueri et al., 2012)	Atherosclerosis (Minamino et al., 2002), HfpEF (Gevaert et al., 2017), hematopoietic ageing (Poulos et al., 2017), AAA, vascular stiffness (Durik et al., 2012)
Vascular smooth muscle cells	prelamin A↑ (Ragnauth et al., 2010), SA β-gal↑ (Matthews et al., 2006), p16↑ (Matthews et al., 2006), p21↑ (Chen et al., 2016), Cyclin D1↑ (Burton et al., 2007), Sirt1↓ (Thompson et al., 2014), PDGFRα↑ (Vazquez-Padron et al., 2004), TRF2↓ (Wang et al., 2015), telomere attrition (Cafueri et al., 2012), glycolysis↑ (Docherty et al., 2018)	Atherosclerosis and plaque vulnerability (Kunieda et al., 2006; Matthews et al., 2006; Wang et al., 2015), neointima formation (Vazquez-Padron et al., 2004), AAA (Chen et al., 2016; Liao et al., 2000), TAA (Watson et al., 2017), vascular stiffness (Durik et al., 2012), artery calcification (Nakano-Kurimoto et al., 2009)
Cardiomyocytes	p16↑ (Chimenti et al., 2003), MMP 9↑, TAF↑ (Anderson et al., 2019)	Cardiac ageing (myocardial hypertrophy and fibrosis) (Anderson et al., 2019; Walaszczyk et al., 2019) and heart failure (Chimenti et al., 2003)
Myofibroblasts	SA β-gal↑, p21↑, p16↑ (Meyer et al., 2016)	Anti-myocardial fibrosis (Meyer et al., 2016)
Fibroblasts	FoxO4↑ (Baar et al., 2017), DPP4↑ (Kim et al., 2017), PAI-1↑ (Goldstein et al., 1994; Murano et al., 1991), Sirt1↓, DNase2↓, TREX1↓ (Takahashi et al., 2018)	HPGS/Atherosclerosis
Adipocytes	Osteopontin↑ (Sawaki et al., 2018), TAF↑ (Xu et al., 2018), γ-H2AX↑, p21↑, Sirt1↓, Sirt3↓ (Lefranc et al., 2019)	Myocardial fibrosis/dysfunction↑ (Sawaki et al., 2018), anticontractile capacity↓ (Lefranc et al., 2019)
Macrophages	SA β-gal↑	Atherosclerosis (Childs et al., 2016)
T cell	Telomere shortening	Atherosclerosis (Samani et al., 2001) and myocardial infarction (Brouilette et al., 2003)
Endothelial progenitor cells	SA β-gal↑ (Hill et al., 2003)	Endothelial dysfunction (Hill et al., 2003)
Cardiac progenitor cells	p16↑, SA β-gal↑, γH2AX↑ (Lewis-McDougall et al., 2019)	Impaired regeneration and cardiac function in infarcted or aged heart (Lewis-McDougall et al., 2019)

AAA, abdominal aortic aneurysm; DNase2, deoxyribonuclease 2; DPP4, dipeptidyl peptidase 4; HFpEF, heart failure with a preserved ejection fraction; PAI-1, plasminogen activator inhibitor-1; TAF, telomere-associated foci; TREX1, DNA 3’ repair exonuclease 1; TRF2, telomeric repeat-binding factor-2; TSP1, thrombospondin 1. Refer to the text for the expanded form of abbreviations.