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).