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Enhanced bronchial expression of vascular endothelial growth factor and receptors (Flk-1 and Flt-1) in patients with chronic obstructive pulmonary disease.
Thorax. 2005 Feb; 60(2):106-13.T

Abstract

BACKGROUND

Ongoing inflammatory processes resulting in airway and vascular remodelling characterise chronic obstructive pulmonary disease (COPD). Vascular endothelial growth factor (VEGF) and its receptors VEGFR-1 (Flt-1) and VEGFR-2 (KDR/Flk-1) could play a role in tissue remodelling and angiogenesis in COPD.

METHODS

The cellular expression pattern of VEGF, Flt-1, and KDR/Flk-1 was examined by immunohistochemistry in central and peripheral lung tissues obtained from ex-smokers with COPD (forced expiratory volume in 1 second (FEV(1)) <75% predicted; n = 14) or without COPD (FEV(1) >85% predicted; n = 14). The immunohistochemical staining of each molecule was quantified using a visual scoring method with grades ranging from 0 (no) to 3 (intense).

RESULTS

VEGF, Flt-1, and KDR/Flk-1 immunostaining was localised in vascular and airway smooth muscle (VSM and ASM) cells, bronchial, bronchiolar and alveolar epithelium, and macrophages. Pulmonary endothelial cells expressed Flt-1 and KDR/Flk-1 abundantly but not VEGF. Bronchial VEGF expression was higher in microvascular VSM cells and ASM cells of patients with COPD than in patients without COPD (1.7 and 1.6-fold, p<0.01, respectively). VEGF expression in intimal and medial VSM (1.7 and 1.3-fold, p<0.05) of peripheral pulmonary arteries associated with the bronchiolar airways was more intense in COPD, as was VEGF expression in the small pulmonary vessels in the alveolar region (1.5 and 1.7-fold, p<0.02). In patients with COPD, KDR/Flk-1 expression was enhanced in endothelial cells and in intimal and medial VSM (1.3, 1.9 and 1.5-fold, p<0.02) while endothelial Flt-1 expression was 1.7 times higher (p<0.03). VEGF expression was significantly increased in bronchiolar and alveolar epithelium as well as in bronchiolar macrophages (1.5-fold, p<0.001). The expression of VEGF in bronchial VSM and mucosal microvessels as well as bronchiolar epithelium was inversely correlated with FEV(1) (r<-0.45; p<0.01).

CONCLUSIONS

VEGF and its receptors Flt-1 and KDR/Flk-1 may be involved in peripheral vascular and airway remodelling processes in an autocrine and/or paracrine manner. This system may also be associated with epithelial cell viability during airway wall remodelling in COPD.

Authors+Show Affiliations

Department of Pharmacology, Erasmus MC, University Medical Center, Dr Molewaterplein 50, 3015 GE Rotterdam, The Netherlands.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15681497

Citation

Kranenburg, A R., et al. "Enhanced Bronchial Expression of Vascular Endothelial Growth Factor and Receptors (Flk-1 and Flt-1) in Patients With Chronic Obstructive Pulmonary Disease." Thorax, vol. 60, no. 2, 2005, pp. 106-13.
Kranenburg AR, de Boer WI, Alagappan VK, et al. Enhanced bronchial expression of vascular endothelial growth factor and receptors (Flk-1 and Flt-1) in patients with chronic obstructive pulmonary disease. Thorax. 2005;60(2):106-13.
Kranenburg, A. R., de Boer, W. I., Alagappan, V. K., Sterk, P. J., & Sharma, H. S. (2005). Enhanced bronchial expression of vascular endothelial growth factor and receptors (Flk-1 and Flt-1) in patients with chronic obstructive pulmonary disease. Thorax, 60(2), 106-13.
Kranenburg AR, et al. Enhanced Bronchial Expression of Vascular Endothelial Growth Factor and Receptors (Flk-1 and Flt-1) in Patients With Chronic Obstructive Pulmonary Disease. Thorax. 2005;60(2):106-13. PubMed PMID: 15681497.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Enhanced bronchial expression of vascular endothelial growth factor and receptors (Flk-1 and Flt-1) in patients with chronic obstructive pulmonary disease. AU - Kranenburg,A R, AU - de Boer,W I, AU - Alagappan,V K T, AU - Sterk,P J, AU - Sharma,H S, PY - 2005/2/1/pubmed PY - 2005/2/23/medline PY - 2005/2/1/entrez SP - 106 EP - 13 JF - Thorax JO - Thorax VL - 60 IS - 2 N2 - BACKGROUND: Ongoing inflammatory processes resulting in airway and vascular remodelling characterise chronic obstructive pulmonary disease (COPD). Vascular endothelial growth factor (VEGF) and its receptors VEGFR-1 (Flt-1) and VEGFR-2 (KDR/Flk-1) could play a role in tissue remodelling and angiogenesis in COPD. METHODS: The cellular expression pattern of VEGF, Flt-1, and KDR/Flk-1 was examined by immunohistochemistry in central and peripheral lung tissues obtained from ex-smokers with COPD (forced expiratory volume in 1 second (FEV(1)) <75% predicted; n = 14) or without COPD (FEV(1) >85% predicted; n = 14). The immunohistochemical staining of each molecule was quantified using a visual scoring method with grades ranging from 0 (no) to 3 (intense). RESULTS: VEGF, Flt-1, and KDR/Flk-1 immunostaining was localised in vascular and airway smooth muscle (VSM and ASM) cells, bronchial, bronchiolar and alveolar epithelium, and macrophages. Pulmonary endothelial cells expressed Flt-1 and KDR/Flk-1 abundantly but not VEGF. Bronchial VEGF expression was higher in microvascular VSM cells and ASM cells of patients with COPD than in patients without COPD (1.7 and 1.6-fold, p<0.01, respectively). VEGF expression in intimal and medial VSM (1.7 and 1.3-fold, p<0.05) of peripheral pulmonary arteries associated with the bronchiolar airways was more intense in COPD, as was VEGF expression in the small pulmonary vessels in the alveolar region (1.5 and 1.7-fold, p<0.02). In patients with COPD, KDR/Flk-1 expression was enhanced in endothelial cells and in intimal and medial VSM (1.3, 1.9 and 1.5-fold, p<0.02) while endothelial Flt-1 expression was 1.7 times higher (p<0.03). VEGF expression was significantly increased in bronchiolar and alveolar epithelium as well as in bronchiolar macrophages (1.5-fold, p<0.001). The expression of VEGF in bronchial VSM and mucosal microvessels as well as bronchiolar epithelium was inversely correlated with FEV(1) (r<-0.45; p<0.01). CONCLUSIONS: VEGF and its receptors Flt-1 and KDR/Flk-1 may be involved in peripheral vascular and airway remodelling processes in an autocrine and/or paracrine manner. This system may also be associated with epithelial cell viability during airway wall remodelling in COPD. SN - 0040-6376 UR - https://www.unboundmedicine.com/medline/citation/15681497/Enhanced_bronchial_expression_of_vascular_endothelial_growth_factor_and_receptors__Flk_1_and_Flt_1__in_patients_with_chronic_obstructive_pulmonary_disease_ L2 - https://thorax.bmj.com/lookup/pmidlookup?view=long&amp;pmid=15681497 DB - PRIME DP - Unbound Medicine ER -