Table 1.

Endothelial mechanism in COPD. In the lung, the endothelium has a critical position and must function properly to ensure the balance of the whole system. The endothelial activity plays a key role in the development of the disease.

Transendothelial migration (TEM)	TEM involves the migration of neutrophils through the endothelial cell, bypassing the normal paracellular route which involves its junction [52]. This mechanism appears to be upregulated in patients with COPD, with a unique pathway [13,52]. Since NO levels have the purpose of regulating neutrophil–endothelial interactions, lower levels of NO probably play a role in stimulating the TEM route [53]. In addition, ICAM-1, which is actively involved in TEM, seems to be inversely related to lung function and proportionally related to the severity of emphysema on CT scans [13].
Endothelial apoptosis	Apoptosis is a process regulated by the cell in response to various stimuli or triggers, such as DNA damage or oxidative stress [54]. Initial clinical trials suggested pulmonary vascular endothelial cell apoptosis may plays a significant role in emphysema development [13,54,55].
Endothelial cell senescence	In patients with COPD, especially smokers, oxidative stress is obviously more elevated as a result of many altered mechanisms. Consequently, this results in an accelerated senescence, which is related to BPCO development and to increases in systemic inflammation [56]. Interestingly, it has been proven that corticosteroids appear to have beneficial role in protecting pulmonary endothelial cells from cell senescence [56].
VEGF	VEGF is released in response to hypoxia and plays the role of a growth factor for endothelial cells. VEGF expression prevents endothelial cell apoptosis and induces cell proliferation [13]. Levels of VEGF have been shown to be decreased in patients with COPD [13,28].