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Pulmonary arterial hypertension (PAH) is an uncommon disorder that may be hereditable, idiopathic or associated with conditions like drug exposure, connective tissue disease, HIV infection or congenital heart disease. Familial disease are usually due to mutations in the bone morphogenic protein receptor type 2 (BMPR2), activin-like kinase-type 1 (ALK1) and endoglin (ENG). Functional and structural changes in the pulmonary vasculature lead to increased pulmonary vascular resistance. Vascular remodeling involves endothelial dysfunction, activation of fibroblasts and smooth muscle cells and recruitment of circulating progenitor cells. Vasoconstriction has also been shown to affect the remodeling process. Genetics, cellular and molecular basis of PAH are discussed in the paper. [ABSTRACT FROM AUTHOR]

Background/aim: Pulmonary arterial hypertension (PAH) is characterized by maladaptation of pulmonary vasculature which is leading to right ventricular hypertrophy and heart failure. miRNAs play a crucial role in the regulation of many diseases such as viral infection, cancer, cardiovascular diseases, and pulmonary hypertension (PH). In this study, we aimed to investigate the expression pattern of eight human plasma miRNAs (hsa-miR-21-3p, hsa-miR-143- 3p, hsa-miR-138-5p, hsa-miR-145-3p, hsa-miR-190a, hsa-miR-204-3p, hsamiR-206, hsa-miR-210-3p) in mild-to-severe PH patients and healthy controls. Materials and methods: miRNAs were extracted from the peripheral plasma of the PH patients (n: 44) and healthy individuals (n: 30) by using the miRNA Isolation Kit. cDNA was synthesized using All in-One First strand cDNA Synthesis Kit. Expression of the human plasma hsa-miR- 21-3p, hsa-miR-143-3p, hsa-miR-138-5p, hsa-miR-145-3p, hsa-miR-190a, hsa-miR-204- 3p, hsa-miR-206, hsa-miR210-3p, and miRNAs were analyzed by qRT-PCR. Results: According to our results, in PH patients hsa-miR-21-3p and hsa-miR-143-3p expression levels were decreased by 4.7 and 2.3 times, respectively. No significant changes were detected in hsa-miR-138-5p, hsa-miR-145-3p, hsa-miR-190a, hsa-miR-204-3p, hsamiR-206, and hsa-miR-210-3p expression levels between PH and control groups. In addition, considering the severity of the disease, it was observed that the decrease in miR-138, miR-143, miR-145, miR-190, mir-204, mir-206 and miR-208 expressions was significant in patients with severe PH. Conclusion: In the early diagnosis of PAH, hsa-miR-21-3p and especially hsa-miR-143-3p in peripheral plasma can be considered as potential biomarkers. [ABSTRACT FROM AUTHOR]

Objective: Germline mutations in the bone morphogenetic protein receptor type-2 (BMPR2) gene are considered to be a major risk factor for pulmonary arterial hypertension (PAH). BMPR2 mutations have been reported in 10%-20% of idiopathic PAH and in 80% of familial PAH cases. The aim of this study was to evaluate the frequency of mutations in the serine/threonine kinase domain of the BMPR2 gene in a group of patients from a single PAH referral center in Turkey. Methods: This cross-sectional study used a DNA-sequencing method to investigate BMPR2 mutations in the serine-threonine-kinase domain in 43 patients diagnosed with PAH [8 with idiopathic PAH and 35 with congenital heart disease (CHD)] from a single PAH referral center. Patients were included if they had a hemodynamically measured mean pulmonary arterial pressure of >25 mm Hg with a mean pulmonary capillary wedge pressure of ⩽15 mm Hg. Patients with severe left heart disease and/or pulmonary disease that could cause pulmonary hypertension were excluded. Associations between categoric variables were determined using the chi-square test. Differences between idiopathic and CHD-associated PAH groups were compared with the unpaired Student's t-test for continuous variables. Results: We detected a missense mutation, [p.C347Y (c.1040G>A)], in one patient with idiopathic PAH in exon 8 of the BMPR2 gene. The mutation was detected in a 27-year-old female with a remarkable family history for PAH. She had a favorable response to endothelin receptor antagonists. No mutations were detected in the exons 5-11 of the BMPR2 gene in the PAH-CHD group. Conclusion: A missense mutation was detected in only one of the eight patients with idiopathic PAH. The BMPR2 missense mutation rate of 12.5% in this cohort of Turkish patients with idiopathic PAH was similar to that seen in European registries. The index patient was a young female with a family history remarkable for PAH; she had a good long-term response to PAH-specific treatment, probably due to the early initiation of the treatment. Genetic screening of families affected by PAH might have great value in identifying the disease at an early stage. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to evaluate the associations of sonographic and sonoelastographic parameters with clinical cardiac parameters, as well as to assess their value in predicting survival in patients with pulmonary arterial hypertension (PAH). Methods: Thirty-six patients with PAH and normal liver function were prospectively enrolled in this prospective study along with 26 healthy controls, all of whom underwent ultrasound and point shear wave elastography examinations. Additionally, the portal vein pulsatility index (PVPI), inferior vena cava collapsibility index, and clinical cardiac variables were obtained in PAH patients. The values of hepatic (LVs) and splenic shear wave velocity (SVs) were compared between PAH patients and controls. The relationships between all sonographic and clinical parameters in the PAH patients were analyzed. Furthermore, their prognostic value in predicting survival was investigated. Results: LVs values in PAH patients (median, 1.62 m/s) were significantly higher than in controls (median, 0.99 m/s), while no significant difference was observed in SVs values. Patients with higher grades of tricuspid regurgitation (TR) had significantly different values of PVPI (P=0.010) and sonoelastographic parameters (P<0.001 for LVs and P=0.004 for SVs) compared to those with less severe TR. Tricuspid annular plane systolic excursion values were the only investigated parameter found to be associated with survival (hazard ratio, 0.814; 95% confidence interval, 0.694 to 0.954; P=0.011). Conclusion: Our results demonstrated a direct association between cardiac congestion (i.e., the severity of TR) and liver stiffness, which should be kept in mind during the assessment of fibrosis in patients with PAH. [ABSTRACT FROM AUTHOR]

Background Right ventricular ( RV) dysfunction is a major determinant of outcomes in patients with pulmonary arterial hypertension ( PAH), although the optimal measure of RV function is poorly defined. We evaluated the utility of RV free-wall speckle tracking strain as an assessment tool for RV function in patients with PAH who are already under specific treatment compared with conventional echocardiographic parameters and investigated the relationship of RV free-wall strain with clinical hemodynamic parameters of RV performance. Methods Right ventricular free-wall strain was evaluated in 92 patients (Group-1 and Group-4 pulmonary hypertension) who were on PAH-specific treatment for at least 3 months. Right atrial ( RA) area, RV FAC, TAPSE, tricuspid S, functional class, 6-minute walking distance, and NT-pro BNP were studied. The mean duration of follow-up was 222±133 days. Results All patients were under PAH-specific treatment, and mean RV free-wall strain was −13.16±6.3%. RV free-wall strain correlated well with functional class ( r=.312, P=.01), NT-pro BNP ( r=.423, P=.0001), RA area ( r=.427, P=.0001), FAC ( r=−.637, P=.0001), TAPSE ( r=−.524, P=.0001), tricuspid S ( r=−.450, P=.0001), 6-minute walking distance ( r=−.333, P=.002). RV free-wall strain significantly correlated with all follow-up adverse events, death, and clinical right heart failure ( RHF) ( P=.04, P=.03, P=.02, respectively). According to the receiver operator characteristic analysis, the cutoff value for RV free-wall strain for the development of clinical RHF was −12.5% (sensitivity: 71%, specificity: 67%) and for all cardiovascular adverse events (death included) was −12.5% (sensitivity: 54%, specificity: 64%). Conclusion Assessment of RV free-wall strain is a feasible, easy-to-perform method and may be used as a predictor of RHF, clinical deterioration, and mortality in patients already under PAH-specific treatment. [ABSTRACT FROM AUTHOR]