Table 1 Effect of ageing on angiogenesis-related factors

ECM

 Collagen

Longer and thicker fibrillar structures; formation and cross-linking by AGEs

Decreased integrity of the vascular network and reduced vascular sprouting

[21, 24, 28]

 Elastin

Thinner, more fractured, and disordered structure, with a higher degree of calcification

Increased ECM stiffness and interference with angiogenesis

[37,38,39]

 Laminin

Increased LAMB1 and decreased LAMB2 expression

Impaired EC formation and migration, disrupting vascular cord formation

[42]

 FN

Glycation and changes in globular structure

Increased ECM stiffness, disrupting vascular cord formation

[45, 78]

 Perlecan

Decreased levels

Disruption of vascular morphogenesis

[47]

 Decorin

Shorter GAG length

Increased ECM stiffness, hindering angiogenesis

[51, 52]

 HA

Decreased levels

Increased ECM stiffness, hindering angiogenesis

[47]

MMPs and inhibitors

 MMP-1

Unknown

Unknown

 MMP-2

Increased levels

Endovascular thickening and remodelling

[142]

 MMP-3

Unknown

Unknown

 MMP-7

Increased levels

Promotion of fibrosis

[143]

 MMP-8

No significant change

–

[143]

 MMP-9

Increased levels

Enhanced proliferation and migration of parietal cells; intimal hyperplasia, leading to atherosclerosis; upregulation of endothelial statin, impairing angiogenesis

[144, 145]

 MMP-12

Decreased levels

Reducing arterial elastin and altering axial arterial mechanics

[146]

 MT1-MMP

Decreased levels

Inhibiting of lumen formation and reducing of pericyte chemotactic proliferation in ECs

[142]

 TIMP-1

Increased levels

Inhibiting the activity of MMPs, imbalance of MMPs and TIMPs

[143]

 TIMP-2

Increased levels

Inhibiting the activity of MMP-2 and MT1-MMP, impairing ageing-related angiogenesis

[142]

 TIMP-3

Increased levels

Inhibiting normal matrix remodelling, limiting neovascularisation

[147]

Angiogenic growth factor

 VEGF

Decreased levels

Imbalance of pro- and anti-angiogenic factors, impairing angiogenesis

[73, 148, 149]

 PDGF

Decreased levels

[150]

 FGF-2

Decreased levels

[151]

 TGF-β

Decreased levels

[152]

 Ang-1, -2

No change

[148]

Anti-angiogenic growth factor

 TSP-1

Increased levels

Imbalance of pro- and anti-angiogenic factors, impairing angiogenesis

[73, 153]

 TSP-2

Increased levels

[74]

 TNF-α

Increased levels

[154]