Circulating tissue factor procoagulant activity is elevated in stable moderate to severe chronic obstructive pulmonary disease

Abstract

Introduction-Chronic obstructive pulmonary disease (COPD) patients have increased risk for cardiovascular mortality and venous thromboembolism. Tissue factor (TF) is the physiological initiating mechanism for blood coagulation and is pro-inflammatory.

Gene promoter methylation is associated with lung function in the elderly: The normative aging study

“…The F3 gene encodes coagulation factor III, a cell surface glycoprotein with major roles in initiating the blood coagulation cascade, chemokine production, 25 pro-inflammatory effects and innate immunity. 25,26 There is no experimental data to support the assumption that methylation in F3 promoter regulates the gene. However, the sequence we analyzed was previously suggested to have that role based on sequence characteristics.…”

“…28,29 Consistent with our results, higher F3 levels in whole blood have been shown in patients with COPD compared with healthy subjects. 26 Moreover, inflammation also promotes coagulation which accentuates the (POU2F2, BCL3, STAT1, PU.1, SP1, Inil, EBF1, HEY1, BATF, BAF155, TAF1 and STS2). This might help to explain the differences we saw between position 3 and positions 1-2 (Table S4).…”

Lung Diseases - Selected State of the Art Reviews

“…Whether this increased velocity of shortening is innate or acquired due to asthma in humans remains to be determined. Two mechanisms have been suggested to be responsible for the observed increased velocity of shortening in asthmatic ASM: 1-The increased expression of myosin light chain kinase (MLCK) (3,16,133); and 2-a preponderant expression of the faster cycling smooth muscle myosin heavy chain (smMHC) isoform B over the slower cycling smMHC isoform A (reviewed in (132)). MLCK is a enzyme capable of phosphorylating the regulatory myosin light chain (rMLC), which is a necessary step required for actin-activation of myosin ATPase activity and the subsequent binding and pivotal of the cross-bridges on the actin filaments.…”

“…In accordance to this assertion, the ratio of the isoforms correlates with the level of airway responsiveness in rats; i.e., hyperresponsive animals expressed more of the B than the normo-responsive animals (73). The mRNA expression of the B isoform is also overexpressed in human asthmatics (133). Taken together, the amount and the velocity of shortening are potentially important factors determining the level of airway responsiveness.…”

“…Thrombin has been implicated in a number of pulmonary fibrotic diseases such as acute lung injury (ALI) 124,125 acute respiratory distress syndrome (ARDS) 126 , interstitial lung disease (ILD) 127,128 and IPF 127,[129][130][131][132] and IPF BAL fluid thrombin has been shown to promote fibroblast proliferation 131 . In COPD, elevated procoagulant activity has been observed in the serum of patients with moderate to severe disease 133 . Animal models of fibrosis have strengthened the connection between thrombin and fibrosis.…”