Table 2. Angiogenesis discovery milestones.

Year	Discovery	References
1794	First observation that new blood vessels originate from pre-existing ones and vascularity is proportional to tissue metabolic requirements	Hunter (1794)
1971	Angiogenesis is found to be necessary in tumour growth and inhibition of angiogenesis can be helpful in anticancer therapy	Folkman (1971)
1980	Discovery of Ca2+-dependent endothelial-derived relaxing factor (EDFR), which is now recognised as nitric oxide (NO•)	Furchgott & Zawadzki (1980)
1989	Discovery of vascular endothelial growth factor (VEGF) –a key signalling molecule in angiogenesis	Ferrara & Henzel (1989)
1990	Discovery of first endogenous inhibitor of angiogenesis thrombospondin-1 (TSP-1)	Good et al. (1990)
1992	Discovery of hypoxia-inducible factor-1 (HIF-1), the major regulator of skeletal muscle and bone angiogenesis	Semenza & Wang (1992)
1992	Identification of VEGF receptors, i.e., fms-like tyrosine kinase receptor (Flt-1) and fetal liver tyrosine kinase receptor (KDR)	de Vries et al. (1992), Terman et al. (1992)
1993	First observation that inhibition of VEGF decreases density of vessels and suppresses tumour growth in vivo	Kim et al. (1993)
2008	Discovery of the mechanism of HIF-independent regulation of exercise-induced skeletal muscle angiogenesis via peroxisome proliferator-activated receptor- γ coactivator (PGC-1α)	Arany et al. (2008)
2014	Discovery of type H and L ECs in bone and the demonstration that type H ECs are involved in bone angiogenesis	Kusumbe, Ramasamy & Adams (2014)

Notes.

ECs

endothelial cells

EDFR

Ca²⁺-dependent endothelial-derived relaxing factor

Flt-1

fms-like tyrosine kinase receptor (VEGF receptor 1)

HIF-1

hypoxia-inducible factor-1

KDR

fetal liver tyrosine kinase receptor (VEGF receptor 2)

NO^•

nitric oxide

PGC-1α

peroxisome proliferator-activated receptor- γ coactivator

TSP-1

thrombospondin-1

VEGF

vascular endothelial growth factor