Effect of iloprost on biomarkers in patients with congenital heart disease‐pulmonary arterial hypertension

Abstract

SummarySome biomarkers play important roles in the endothelial dysfunction of patients with pulmonary arterial hypertension (PAH), including nitric oxide (NO), endothelin‐1 (ET‐1), asymmetric dimethylarginine (ADMA), galectin‐3 (Gal‐3), B‐type natriuretic peptide (BNP), and uric acid (UA). However, studies on these biomarkers in pulmonary artery blood in congenital heart disease‐PAH (CHD‐PAH) and the effect of iloprost on the regulation of biomarkers are lacking. This study investigated potential CHD‐PAH biomarkers and their association with the severity of disease. The effect of iloprost on the regulation of these biomarkers was also studied. A total of 31 patients with CHD‐PAH were enrolled. Seven with positive effects of iloprost (the average reduction in mPAP 11.13±1.73 mm Hg) and 19 with negative effects of iloprost (the average reduction in mPAP 4.21±4.87 mm Hg; iloprost positive group [IPG] vs iloprost negative group [ING], P<.01) and five age‐matched controls were studied. The pulmonary artery blood sample was collected before and after inhaling iloprost, and the plasma concentrations of Gal‐3, ADMA, ET‐1, and NO were measured. A significant positive linear relationship was observed between mPAP and plasma ET‐1, BNP, ADMA, and UA levels in all patients with CHD‐PAH. ET‐1, ADMA, BNP, and UA levels had a significant linear relationship with mean pulmonary arterial pressure, which could be used to predict the severity of CHD‐PAH. ET‐1 might be a potential biomarker to pre‐evaluate the effect of iloprost on CHD‐PAH. Iloprost could affect the expression of Gal‐3 and, therefore, the process of fibrosis could be influenced by iloprost.

The Role of Galectin-3 in Predicting Congenital Heart Disease Outcome: A Review of the Literature

“…While taking into consideration the potential modulation of Gal-3 for the prevention of myocardial fibrosis, one study and two randomized controlled trials (RCTs) assessed the effect of an aldosterone antagonist agent, eplerenone, and a prostacyclin analogue, iloprost, on its circulating levels [ 98 , 99 , 100 ], while, in one RCT, eplerenone did not significantly influence the Gal-3 levels in adults with a childhood diagnosis of ToF or complete TGA. In another one, which enrolled adults with a history of TGA correction, a decrease in Gal-3 was found after one year of treatment [ 98 , 100 ].…”

“…In another study, iloprost inhalation did significantly lower the Gal-3 levels in patients with CHD and pulmonary artery hypertension. Thus, iloprost might influence myocardial fibrotic processes through Gal-3 modulation [ 99 ].…”

Pulmonary arterial hypertension associated with congenital heart disease: An omics study

“…The clinical classification of PAH-CHD includes Eisenmenger's syndrome, PAH associated with prevalent systemic-to-pulmonary shunts, PAH with small/coincidental defects, and PAH after defect correction (14). PAH-CHD can induce progressive proliferation and migration of pulmonary vascular smooth muscle cells as well as permanent pulmonary vascular remodeling (15). Although there is a decreasing trend in the mortality of PAH-CHD, the symptoms of PAH-CHD can still worsen during a person's lifetime, and PAH is incurable (16).…”

“…The pathogenesis of complex diseases such as PAH-CHD can be studied at different omics levels. Many of the methods currently used to assess the severity of PAH and evaluate treatment outcomes (e.g., right heart catheterization, cardiac function class, and 6-min walk distance) have significant limitations (15). Without early diagnosis and appropriate treatment, the survival rate of PAH-CHD is low.…”

Identification of potential serum biomarkers for congenital heart disease children with pulmonary arterial hypertension by metabonomics

“…Biomarkers can be detected from blood, urine, feces and other body fluids, and the detection is convenient, low cost and non-invasive, which provides a new strategy for early diagnosis and treatment in the field of CHD-PAH. In recent years, studies have shown that brain natriuretic peptide (BNP), N-terminal pro- brain natriuretic peptide (NT-proBNP), asymmetric dimethylarginine (ADMA), and vascular endothelial growth factor (VEGF) may be potential diagnostic biomarkers for PAH-CHD, but the specificity of these biomarkers is still controversial [ 6 , 7 ]. Therefore, it is of great clinical significance to screen suitable non- invasive biomarkers for early diagnosis of PAH-CHD from CHD in infants and young children.…”