2.5 The regulation of angiogenesis
In recent years, there is increasing evidence that pulmonary vascular injury has become a major manifestation of BPD. Jing et al.found that early caffeine treatment increased cAMP levels in a hyperoxicmodel of lung injury, improved endothelial nitric oxide synthase (eNOS) activity by inhibiting the degradation of GTP-cyclohydrolase-1, improved the bioavailability of tetrahydrobiopterin(BH4), and improved alveolar structure and vascular function72. In addition, Dumpa et al.used male miceto show that caffeine can improve pulmonary vascular remodeling in response to hyperoxia by increasing the vascular surface area of small pulmonary arteries and by inhibiting smooth muscle proliferation73. However, additional studies have found that caffeine inhibits embryonic angiogenesis74; therefore, furtherstudies are required to support the protective effects of caffeine against pulmonary vascular injury.
In summary, the clinical benefits of caffeine have been confirmed, although the molecular mechanisms responsible for its action remain controversial and are still being investigated.Currently, research is limited to five aspects: anti-inflammatory, antioxidant, anti-apoptotic, and anti-fibrotic effects, and the regulation of angiogenesis. Caffeine can act as a neurostimulant, thus leading to severe restrictions in the clinical research process in many countries. In recent years, caffeine has been shown to be protective against both Parkinson’s disease75and colorectal cancer76by regulating flora and autophagy; however, there is still significant scope for investigating the effect of caffeine on BPD. This condition affects the long-term survival of newborns; consequently, we need to consider this disease carefully and find effective solutions for prevention and treatment in order to promote human development.