Objective: To study if there is an aryl-hydrocarbon receptor (AHR) expression in patients of pulmonary arterial hypertension associated with congenital heart disease (CHD-PAH) and to explore if the amount of AHR expression related to pulmonary vascular remodeling.
Methods:A total of 32 CHD-PAH patients diagnosed by echocardiography and right heart catheterization for surgical repair were enrolled, and the lung tissue biopsy was performed during the operation. The pulmonaryAHR was detected by immunolfuorescence assay, the ratios of vessel wall area/total area (WA/TA) and vessel wall thickness/vessel external diameter (WD/TD) of small pulmonary arteries were calculated with the imaging software, the mRNA expression of AHR, hypoxia-inducible factor-1α (HIF-1α), aryl-hydrocarbon receptor nuclear translocator (ARNT) and vascular endothelial growth factor (VEGF) were examined by RT-PCR. In addition, blood level of AHR was measured by ELISA.
Results: There was AHR expression in pulmonary tissue in all 32 patients. And AHR mRNA expressions were positively related to mPAP (r=0.809,P<0.001), WA/TA (r=0.723,P<0.001), WD/TD (r=0.746,P<0.001); and positively related to mRNA expressions of HIF-1α (r=0.889,P<0.001), ARNT (r=0.738,P<0.001), VEGF (r=0.822,P<0.001). Pulmonary tissue VEGF mRNA expressions were positively related to mPAP (r=0.739,P<0.001), WD/TD (r=0.702,P<0.001) and WA/TA (r=0.657,P<0.001). Blood levels of AHR were positively related to mPAP (r=0.754,P<0.001), WD/TD (r=0.754, P<0.001) and WA/TA (r=0.739,P<0.001).
Conclusion: AHR might be involved in pulmonary vascular remodeling in CHD-PAHpatients.

BACKGROUND: Coronary artery disease (CAD) is the commonest cause of heart failure (HF), whereas pulmonary hypertension (PH) has not been established or reported in this patient population. Therefore, we assessed the prevalence, risk factors, and survival in CAD-associated HF (CAD-HF) complicated with PH. METHODS: Symptomatic CAD-HF patients were continuously enrolled in this prospective, multicenter registry study. Echocardiography, coronary arteriography, left and right heart catheterization (RHC), and other baseline clinical data were recorded. Patients were followed up and their survival was recorded. RESULTS: One hundred and eighty-two CAD-HF patients were enrolled, including 142 with HF with a preserved ejection fraction (heart failure with preserved ejection fraction [HFpEF]; left ventricular ejection fraction [LVEF] ≥50%) and 40 with a reduced ejection fraction (heart failure with reduced ejection fraction [HFrEF]; LVEF < 50%). PH was diagnosed with RHC in 77.5% of patients. Patients with PH showed worse hemodynamic parameters and higher mortality. HFrEF-PH patients had worse survival than HFpEF-PH patients. CAD-HF patients with an enlarged left ventricular end-diastolic diameter and reduced hemoglobin were at higher risk of PH. Nitrate treatment reduced the risk of PH. Elevated creatinine and mean pulmonary arterial pressure (mPAP), diastolic pressure gradient (DPG) ≥7 mmHg, and previous myocardial infarction (MI) entailed a higher risk of mortality in CAD-HF patients with PH. CONCLUSIONS: PH is common in CAD-HF and worsens the hemodynamics and survival in these patients. Left ventricle enlargement and anemia increase the risk of PH in CAD-HF. Patients may benefit from nitrate medications. Renal impairment, elevated mPAP, DPG ≥7 mmHg, and previous MI are strong predictors of mortality in CAD-HF-PH patients. TRIAL REGISTRATION ClinicalTrials.gov, NCT02164526.
Coronary Artery Disease/epidemiology* ; Creatinine ; Heart Failure/complications* ; Humans ; Hypertension, Pulmonary/complications* ; Nitrates ; Prevalence ; Prognosis ; Prospective Studies ; Registries ; Risk Factors ; Stroke Volume ; Ventricular Function, Left