Serum Vascular Endothelial Growth Factor and Angiopoietin-2 Are Associated with the Severity of Systemic Inflammation Rather than the Presence of Hemoptysis in Patients with Inflammatory Lung Disease

Abstract

PurposeVascular endothelial growth factor (VEGF) and angiopoietin-2 (Ang-2) are major mediators of angiogenesis and are induced by tissue inflammation and hypoxia. The purpose of this study was to investigate whether serum VEGF and Ang-2 are associated with the presence of hemoptysis and the extent of systemic inflammation in patients with inflammatory lung diseases.Materials and MethodsWe prospectively enrolled 52 patients with inflammatory lung disease between June 2008 and October 2009.ResultsThe median values of VEGF and Ang-2 were 436 pg/mL and 2383 pg/mL, respectively. There was a significant positive correlation between serum Ang-2 and VEGF levels. VEGF levels were not significantly different according to the presence of hemoptysis. C-reactive protein (CRP) and Ang-2 level were significantly higher in patients without hemoptysis (n=26) than in those with hemoptysis (n=26; p<0.001 and p<0.001, respectively). CRP and arterial oxygen tension (PaO2) were significantly correlated with both serum VEGF (p=0.032 and p=0.016, respectively) and Ang-2 levels (p<0.001 and p=0.041, respectively), after adjusting for other factors. Age and the absence of hemoptysis were factors correlated with serum Ang-2 levelsConclusionOur study suggests that serum VEGF and Ang-2 levels are associated with PaO2 and the severity of inflammation rather than the presence of hemoptysis in patients with inflammatory lung diseases. Thus, hemoptysis may not be mediated by increased serum levels of VEGF and Ang-2 in patients with inflammatory lung diseases, and further studies are required to determine the mechanisms of hemoptysis.

Chronic cigarette smoke exposure induces systemic hypoxia that drives intestinal dysfunction

“…Indeed, polycythemia is a well-established consequence of heavy smoking, as the body attempts to compensate for reduced oxygen availability by increasing production of oxygen-carrying RBCs (46)(47)(48). Our finding that serum VEGF, a cytokine and marker of systemic hypoxia (41)(42)(43), is increased in both preclinical and clinical samples in current and former smokers is suggestive that chronic CS exposure can induce long-lasting systemic effects. Increased serum VEGF in CD has been reported previously (44).…”

“…Cigarette smoking and associated systemic hypoxia have been linked to elevated peripheral levels of VEGF in the context of lung and liver disease (41)(42)(43). We found that serum VEGF levels were increased in mice following chronic smoke exposure and smoking cessation and in association with the development of CD-like features ( Figure 10, A and B).…”

Circulating Angiogenic Factors as Biomarkers of Disease Severity and Bacterial Burden in Pulmonary Tuberculosis

“…Hence, VEGF-A might play a role in blood and lymphatic vessel function by regulating cell trafficking, cellular recruitment and inflammation [ 21 , 23 ]. Indeed, serum VEGF-A levels have been shown to be associated with systemic inflammation in inflammatory lung disease [ 24 ] and it has been postulated that VEGF-A might be a major component of the neovascularization of TB granulomas [ 25 ]. Moreover, recent evidence from both zebrafish and rabbit models of mycobacterial infection clearly demonstrate an important role for VEGF-A in the pathogenesis of mycobacterial infection [ 5 , 6 ].…”

Serum angiopoietin-2

“…This is supported by a significant positive correlation between Ang-2 and CRP detected in this study. Moreover, Park et al [26] found that the hypoxic conditions during development of the inflammatory tissue can promote angiogenesis, leading to induced Ang-2 production.…”