Endothelin-1 and functional tissue factor: a possible relationship with severity in primary pulmonary hypertension

Abstract

Although dysfunctional endothelium, vasoconstriction, and in situ thrombosis are characteristics of primary pulmonary hypertension, the role that plasma vasomotor and coagulation factors play in this phenomenon are not completely understood. The aim of this work was to ascertain the diagnostic value of endothelin-1, thrombomodulin, tissue factor, and tissue factor pathway inhibitor, as well as their correlation with endothelial dysfunction in primary pulmonary hypertension patients. We analyzed the plasmatic concentration and chromogenic of the above-mentioned molecules using immunoenzymatic techniques. Patients were divided into responders and nonresponders on the basis of their hemodynamic response to a vasodilator trial. We found a continuous increase in endothelin-1 levels and a continuous decrease in functional tissue factor in the control group, responders, and nonresponders, respectively. Moreover, the patients showed a moderate decrease in thrombomodulin levels compared with the control group, without statistical significance. These results support a previous description of a decrease in thrombomodulin levels in primary pulmonary hypertension patients and suggests that an alteration of endothelin-1 and functional tissue factor could be related to a worsening of endothelial function and, indirectly, with the clinical severity of primary pulmonary hypertension.

Pharmacokinetics and Pharmacodynamics of the ETA‐Selective Endothelin Receptor Antagonist SPP301 in Healthy Human Subjects

“…SPP301 significantly increased plasma ET‐1 levels at the lowest dose of 5 mg. Plasma ET‐1 measurements are useful because plasma concentrations have been found to correlate well with the severity of certain diseases such as primary pulmonary hypertension, cirrhosis, and heart failure 9–11 . The observation that circulations of ET‐1 are increased by the ET A receptor selective antagonist SPP301 in this study is in line with recent observations by others 12 .…”

Exon-based mapping of microarray probes: Recovering differential gene expression signal in underpowered hypoxia experiment

“…The biological relevance of 4 newly identified genes to hypoxia and pulmonary hypertension was suggested by an automated biomedical literature search. The subsequent manual evaluation of PubMatrix citations confirmed involvement of Mig6, F3, Bmp6, and Ndrg1 genes in hypoxia-triggered response [15][16][17][18][19]. Up-regulation of Mig6 expression was validated by real-time RT-PCR.…”

“…Transcriptional changes detected by 26 exon-sharing probe-sets ( Figure 1B) were compared to those detected by the rest of the target-sharing probe-sets (63 probe-sets, Figure 1C) and demonstrated higher correlation of transcriptional changes detected by the exon-sharing probe-sets. The PubMatrix automated biomedical literature search of 24 recovered ( Figure 1A) candidate genes identified several well-known hypoxia or pulmonary hypertension-related genes (Table 1), including Mig6, F3, Bmp6, and Ndrg1 [15][16][17][18][19]. The mouse Mig6 gene was selected for further validation.…”

Activation of the nicotinamide N-methyltransferase (NNMT)-1-methylnicotinamide (MNA) pathway in pulmonary hypertension

“…In our hands, MCT-induced PAH, was featured by progressive increase in right ventricular end-diastolic volume and a significant impairment of the right ventricular ejection fraction, as well as with gradual increase in ET-1 concentration in plasma [28, 33, 34]. Ultrastructural features of an injured pulmonary endothelium, including a thickened basal lamina, with neovascularization and fibrosis, were also compatible with PAH [35–39].…”