Herein, we review the evidence linking endothelial injury to COPD, and the pathways underlying endothelial injury and the "vascular COPD phenotype" including: (1) direct toxic effects of cigarette smoke on endothelial cells; (2) generation of auto-antibodies directed against endothelial cells; (3) vascular inflammation; (4) increased oxidative stress levels in vessels inducing increases in lipid peroxidation and increased activation of the receptor for advanced glycation end-products (RAGE); (5) reduced activation of the anti-oxidant pathways in endothelial cells; (6) increased endothelial cell release of mediators with vasoconstrictor, pro-inflammatory, and remodeling activities (endothelin-1) and reduced endothelial cell expression of mediators that promote vasodilation and homeostasis of endothelial cells (nitric oxide synthase and prostacyclin); and (7) increased endoplasmic reticular stress and the unfolded protein response in endothelial cells.
High CRP levels were associated with younger age, higher body mass index (BMI), chronic obstructive pulmonary disease (COPD), lower peak oxygen consumption and higher endothelin-1 and aldosterone levels.
In contrast to healthy individuals, interstitial prostacyclin levels did not increase during exercise and plasma endothelin-1 levels were higher in the patients with COPD.
Our results show that endothelin-1 gene is implicated in exercise performance in COPD patients and might play a role in adaptation of the cardiopulmonary system to exercise.
Sex hormone alterations and systemic inflammation in a group of male COPD smokers and their correlation with the +138 insA/delA endothelin-1 gene polymorphism. A case-control study.
We performed a case control, genetic study to assess possible associations of two polymorphisms of the ET-1 gene, an adenine insertion (+134 insA/delA) and a guanine to thymine transversion (G198T) with the COPD phenotype and disease severity.