Association Between Circulating CD4+ T Cell Methylation Signatures of Network-Oriented SOCS3 Gene and Hemodynamics in Patients Suffering Pulmonary Arterial Hypertension

Pathogenic DNA methylation changes may be involved in pulmonary arterial hypertension (PAH) onset and its progression, but there is no data on potential associations with patient-derived hemodynamic parameters. The reduced representation bisulfite sequencing (RRBS) platform identified N= 631 differentially methylated CpG sites which annotated to N= 408 genes (DMGs) in circulating CD4(+) T cells isolated from PAH patients vs. healthy controls (CTRLs). A promoter-restricted network analysis established the PAH subnetwork that included 5 hub DMGs (SOCS3, GNAS, ITGAL, NCOR2, NFIC) and 5 non-hub DMGs (NR4A2, GRM2, PGK1, STMN1, LIMS2). The functional analysis revealed that the SOCS3 gene was the most recurrent among the top ten significant pathways enriching the PAH subnetwork, including the growth hormone receptor and the interleukin-6 signaling. Correlation analysis showed that the promoter methylation levels of each network-oriented DMG were associated individually with hemodynamic parameters. In particular, SOCS3 hypomethylation was negatively associated with right atrial pressure (RAP) and positively associated with cardiac index (CI) (vertical bar r vertical bar >= 0.6). A significant upregulation of the SOCS3, ITGAL, NFIC, NCOR2, and PGK1 mRNA levels (qRT-PCR) in peripheral blood mononuclear cells from PAH patients vs. CTRLs was found (P <= 0.05). By immunoblotting, a significant upregulation of the SOCS3 protein was confirmed in PAH patients vs. CTRLs (P < 0.01). This is the first network-oriented study which integrates circulating CD4(+) T cell DNA methylation signatures, hemodynamic parameters, and validation experiments in PAH patients at first diagnosis or early follow-up. Our data suggests that SOCS3 gene might be involved in PAH pathogenesis and serve as potential prognostic biomarker

Psychological counselling interventions to improve perceived quality of life and counter anxiety and depression in pulmonary-arterial-hypertension patients. a clinical trial

Introduction: Pulmonary Arterial Hypertension (PAH) is a rare and progressive disease, frequently associated with a worsening of perceived quality of life as well as anxiety and depression symptomatology. Psychological counselling helps the patient understand the diagnosis and prevent the onset of psychopathologies. This study evaluates the effect of counselling sessions on anxiety and depression as well as the impact on self-reported quality of life in patients with PAH. Methods: Patients with a diagnosis of PAH were recruited at the Monaldi Hospital (Naples). An EQ-5D 3L questionnaire was administered to all patients at baseline (pre-session), three months (post-session) after the last session to patients who received psychological counselling (experimental group, EG) and after the first questionnaire to patients who did not (control group, CG). The EQ-5D index and EQ-VAS score were analysed in both groups. Results: A sample of 50 patients with a PAH diagnosis was evaluated; among them 6% had mild PAH, 66% moderate PAH, and 28% severe PAH. The majority (53%) did not receive psychological counselling. All patients showed no significant difference in EQ-5D index (P > 0.05), EQ-VAS score (P > 0.05), and the anxiety/depression dimension (P>.05) at baseline. However, between pre- and post-session evaluations, the analysis showed a significant change in the EQ-VAS score (P = 0.00) and the anxiety/depression dimension (P = 0.02) in the EG. In the CG, there was a similar change in the anxiety/depression dimension (P = 0.00) but not in the EQ-VAS score (P = 0.05) in CG. The z-test revealed significant intergroup relations, showing that the EG had a 37% increase in perceived quality of life and a 9% reduction in anxiety and depression, while a 12% reduction was observed for the CG’s perceived quality of life and a 44% increase in anxiety and depression. Discussion and Conclusions: This study showed that patients with PAH who received psychological support improved their health-related quality of life by reducing anxiety and depression symptomatology. Our findings highlight the impact of psychological support in the treatment of patients with PAH

Riociguat treatment in patients with chronic thromboembolic pulmonary hypertension: Final safety data from the EXPERT registry

Objective: The soluble guanylate cyclase stimulator riociguat is approved for the treatment of adult patients with pulmonary arterial hypertension (PAH) and inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH) following Phase

How to measure peripheral pulmonary vascular mechanics.

Pulmonary hypertension (PH) is initially a disease of the small, peripheral resistance arteries. Changes in these vessels are best assessed by measurement of pulmonary artery pressure at several levels of flow to generate multi-point pressure-flow curves. This approach is superior to the traditional single-point measurement of pulmonary vascular resistance (PVR) because it allows a flow-independent definition of the resistive properties of that portion of the pulmonary vascular bed and also provides information on its distensibility. In animal models, multi-point pressure-flow curves can be obtained using an isolated, ventilated, perfused lung system. Clinically, cardiopulmonary exercise testing (CPET) with non-invasive echocardiography is feasible and provides realistic values of the resistance and peripheral compliance. Together, these values can be used to better understand and screen for PH and exercise-induced PH.Journal ArticleResearch Support, N.I.H. ExtramuralResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe

STRUCTURAL ASSESSMENT OF SANTA MARIA MADDALENA CHURCH IN ISCHIA ISLAND (ITALY) BY EXPERIMENTAL MODAL ANALYSIS UNDER OPERATIONAL CONDITIONS

During the seismic event of 21st August 2017 in Ischia, many masonry churches were damaged. Within the inspected damaged churches, a very interesting case study is represented by Santa Maria Maddalena church, located on the hill of Casamicciola Terme, near to the epicentre. The church of Santa Maria Maddalena can be considered a ‘unicum’, since it was built in 1896, after the catastrophic earthquake of 1883, with a ‘mixed’ structure made mainly of yellow tuff blocks walls strengthened by iron profiles or wooden elements. Several examples of structures made of masonry walls with wooden elements embedded in the wall thickness, i.e. the so called ‘baraccato system’ are present in the island, while the use of iron profiles is rare. The paper is firstly aimed to present the results of detailed historical investigation, geometrical survey, damage status analysis and provisional safety assessment after the earthquake of 21st August 2017. These activities were carried out in collaboration with the Campania Regional Directorate for Cultural Heritage (MiBACT). Within such a collaboration, an in situ dynamic test was also performed under operational conditions. The set-up and the results of this test are here presented in order to point out the main features of the structural system in terms of relevant modal parameters, both at global and local level

Increased pulmonary vascular resistance in early stage systemic hypertension: A resting and exercise stress echocardiography study

Background: In early stage uncomplicated systemic hypertension (HT), increased pulmonary vascular resistance (PVR) has been reported at rest, but more rarely during exercise. Recently, limits of normal for stress echocardiography in the evaluation of the pulmonary circulation have been better defined. We therefore used this approach to assess the pulmonary circulation in early HT. Methods: One hundred thirteen patients with mild to moderate untreated, uncomplicated HT (blood pressure, 152 ± 19/89 ± 11 mm Hg, heart rate, 70 ± 13 beats per minute) and 345 age- and sex-matched healthy control subjects underwent resting Doppler echocardiography with estimation of mean pulmonary arterial pressure (mPAP), left atrial pressure (LAP), and cardiac output (CO). Measurements were repeated at exercise stress test in 25 patients from each group. Results: At rest, hypertensive patients had normal right and left ventricular structure and function, higher systemic vascular resistance, mPAP (16 ± 5 vs 14 ± 5 mm Hg; P < 0.0001), and PVR (1.3 ± 1.1 vs 1.0 ± 1.2 Wood units; P= 0.006) than control participants, but similar LAP. During exercise, hypertensive patients showed a lower maximum workload and CO and higher peak mPAP than control subjects, but a similar increase in LAP. PVR determined according to multipoint mPAP-CO relationships was also higher in hypertensive patients than in control subjects (2.5 ± 1.1 vs 1.5 ± 0.7 mm Hg/L/min; P < 0.05), with no changes in pulmonary resistive vessel distensibility coefficient α (0.012 ± 0.007 vs 0.012 ± 0.010% change in diameter for each mm Hg increase in mPAP). Conclusions: Resting and exercise PVR are increased in uncomplicated HT, without this being related to increased pulmonary venous pressure or resistive vessel stiffness, suggesting an early increase in pulmonary vascular tone.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Gaps of evidence in pulmonary arterial hypertension

The authors discuss the main gas of evidence in the field of diagnosis, risk stratification and therapy of PAH patient

Exercise stress echocardiography for the study of the pulmonary circulation.

Exercise stress tests have been used for the diagnosis of pulmonary hypertension, but with variable protocols and uncertain limits of normal. The pulmonary haemodynamic response to progressively increased workload and recovery was investigated by Doppler echocardiography in 25 healthy volunteers aged 19-62 yrs (mean 36 yrs). Mean pulmonary artery pressure ((Ppa)) was estimated from the maximum velocity of tricuspid regurgitation. Cardiac output (Q) was calculated from the aortic velocity-time integral. Slopes and extrapolated pressure intercepts of (Ppa)-Q plots were calculated after using the adjustment of Poon for individual variability. A pulmonary vascular distensibility alpha was calculated from each (Ppa)-Q plot to estimate compliance. (Ppa) increased from 14+/-3 mmHg to 30+/-7 mmHg, and decreased to 19+/-4 mmHg after 5 min recovery. The slope of (Ppa)-Q was 1.37+/-0.65 mmHg x min(-1) x L(-1) with an extrapolated pressure intercept of 8.2+/-3.6 mmHg and an alpha of 0.017+/-0.018 mmHg(-1). These results agree with those of previous invasive studies. Multipoint (pa)-Q plots were well described by a linear approximation, from which resistance can be calulated. We conclude that exercise echocardiography of the pulmonary circulation is feasible and provides realistic resistance and compliance estimations. Measurements during recovery are unreliable because of rapid return to baseline.Clinical TrialJournal ArticleResearch Support, N.I.H. ExtramuralResearch Support, Non-U.S. Gov'tValidation StudiesSCOPUS: ar.jinfo:eu-repo/semantics/publishe

Stress echocardiography for the study of the pulmonary circulation in Monge's disease

info:eu-repo/semantics/publishe

Echocardiography in Pulmonary Arterial Hypertension: from Diagnosis to Prognosis.

Pulmonary arterial hypertension is most often diagnosed in its advanced stages because of the nonspecific nature of early symptoms and signs. Although clinical assessment is essential when evaluating patients with suspected pulmonary arterial hypertension, echocardiography is a key screening tool in the diagnostic algorithm. It provides an estimate of pulmonary artery pressure, either at rest or during exercise, and is useful in ruling out secondary causes of pulmonary hypertension. In addition, echocardiography is valuable in assessing prognosis and treatment options, monitoring the efficacy of specific therapeutic interventions, and detecting the preclinical stages of disease.JOURNAL ARTICLESCOPUS: re.jinfo:eu-repo/semantics/publishe