Role of serum and tissue vascular remodeling markers in bone loss related to end-stage COPD

Abstract

Aim: to determine associations between vascular remodeling markers and bone composition in end-stage COPD patients with osteopenic syndrome.

Methods: expression of vascular endothelial growth factor (VEGF), endothelin-1, transforming growth factor beta2 (TGFβ2) in blood vessels of striated muscle specimens of 20 subjects were assessed by immunohistochemistry method using immunoperoxidase reaction with monoclonal specific antibodies. Bone mineral density (BMD) at the lumbar spine (LS) and femur neck (FN), bone mineral content (BMC), skeletal muscle mass, expressed as lean mass (LM), serum endothelin-1, VEGF, E-selectin levels were assessed in 48 male patients with end-stage COPD and 36 healthy.

Results: intensity of endothelin-1, TGFβ2, VEGF expression in blood vessels was higher in COPD patients with osteoporosis than in healthy. Serum endothelin-1 and E-selectin were higher in COPD group than in control whereas VEGF levels were lower. Serum E-selectin and endothelin-1 inversely correlated with LS and FN (p<0.001), BMC (p<0.05); there were negative relation between endothelin-1 and LM (p=0.003) and direct association of serum VEGF with LM. Multivariate regression analysis revealed that BMC and serum E-selectin are independently associate with bone loss at the FN (R²=0.679) whereas LM and serum E-selectin (R²=0.524) are predictors of osteoporosis at the LS. Increased serum endothelin-1 and lowered VEGF levels independently related to reduced skeletal LM.

Conclusion: correlations of vascular remodeling markers with body composition in end-stage COPD confirms their contribution to bone damage.

Acknowledgments: This study was supported by a grant from Russian Science Foundation (No. 14-33-00009).