4.1 Pathological modulation of angiogenesis
Angiogenesis is defined as the formation of new capillaries from
established vessels. Physiologically, this process is limited to the
embryonic and postnatal stage and rarely found within healthy adults,
apart from female reproductive organs (Eelen et al. , 2020).
Pathological alterations in angiogenesis are highly diverse in different
organs/tissues. For example, excessive angiogenesis occurs in diabetic
retinopathy/nephropathy, while the angiogenetic capacity is
significantly impaired in cardiac and cerebral tissue of patients with
DM (Okonkwo et al. , 2017). Growth factors like VEGFs play a key
role in promoting vascular growth and remodeling, and they can be
dramatically upregulated by hyperglycaemia, ROS and pro-inflammatory
mediators like TNF-α, but mostly by the lack of oxygen in respective
organs. Local hypoxic conditions activate hypoxia-induced factor
(HIF)-1α and increase the expression of VEGFs (Apte et al. ,
2019). Conditional knockout of HIF-1α attenuated VEGF overproduction and
prevented the development of diabetic retinopathy within mice,
suggesting a crucial role of the HIF-1α/VEGFs pathway in pathological
angiogenesis (Lin et al. , 2011). Vasodilators like NO are
temporarily increased during pregnancy and may promote placental
angiogenesis, but whether this effect persists in adult tissue is
unclear (Umapathy et al. , 2020).