Thus, we hypothesized that salvianolic acid B (Sal-B), a polyphenol in traditional Chinese herbal danshen, is an alveolar structural recovery agent for emphysema by virtue of VEGF stimulation/elevation via activation of Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3), as stimulating lung cell proliferation and migration, and protecting against lung cell death.
Impaired vascular endothelial growth factor (VEGF) signaling is an emerging pathogenic mechanism, thereby proposing a hypothesis that VEGF stimulation/elevation enables recovery from alveolar structural destruction and loss of emphysema.
CDSO3 was spray-dosed to the lung for three weeks (day 1-21) in an in vivo rat model of apoptotic emphysema induced with a VEGF receptor antagonist SU5416.
Therapeutic rHuKGF supplementation improves the deregulated Akt pathway in emphysema, resulting in alveolar cell survival through activation of the endogenous VEGF-dependent cell survival pathway.
Airway administration of VEGF siRNAs induced transient air space enlargement in the mouse lung morphologically resembling the previously reported models of pulmonary emphysema.
It has been shown that blocking the vascular endothelial growth factor (VEGF) signaling pathway leads to apoptosis of lung cells and pulmonary emphysema, and MSC are capable of secreting VEGF.
Excessive neutrophil elastase (NE) activity and altered vascular endothelial growth factor (VEGF) signaling have independently been implicated in the development and progression of pulmonary emphysema.
Oxidative stress upregulates ceramides, proapoptotic signaling sphingolipids that trigger further oxidative stress and alveolar space enlargement, as shown in an experimental model of emphysema due to VEGF blockade.
Repeated CS exposure downregulated bronchiolar expressions of VEGF and both VEGF receptors at various time points prior to the development of emphysema.
In emphysema, pulmonary endothelial cell apoptosis via reduction in VEGF activity causes alveolar epithelial cell apoptosis, thereby increasing the sensitivity of alveolar walls to oxidative stress and proteases.
Experimental models and expression studies suggest that anti-vascular endothelial growth factor (VEGF) receptor strategies may be of use in patients with emphysema, whereas anti-HER1-directed strategies may be more useful in patients with pulmonary mucus hypersecretion, as seen in chronic bronchitis and asthma.
To summarize the critical effects of VEGF on the pulmonary endothelial cell in the pathogenesis of these diseases, the purposes of this review are to (1) discuss the biological activities and intracellular signaling pathways of VEGF in the lung; (2) summarize the regulatory mechanisms involved in VEGF expression; (3)address the effects of VEGF on endothelial cells in hyperoxia-induced and other forms of lung injury; (4) highlight the endothelial effects of VEGF in the pathogenesis of emphysema; and (5) explore the role of VEGF in the pathogenesis of pulmonary arterial hypertension.
VEGF mRNA in AMs demonstrated a 1.8-fold reduction in current smokers compared with nonsmokers in older subjects and, furthermore, a 1.5-fold downregulation in those with emphysema, although there was no difference between current smokers and nonsmokers among the young subjects.
VEGF protein content in lung tissue was reduced in severe emphysema, where reverse transcription-polymerase chain reaction demonstrated a lower proportion of the VEGF189 isoform.