Pulmonary Arterial Hypertension, Pulmonary Arterial Remodeling
Conditions
Keywords
Adaptive immunity, DNA methylome, RNA-sequencing, Network analysis
Brief summary
To identify epigenetic-sensitive modifications and novel biomarkers linked to pathogenesis of pulmonary arterial hypertension (PAH), we will perform the first study analyzing differentially-methylated regions (DMRs) in circulating T cells (CD04+ and CD08+) isolated from peripheral blood of patients undergoing right heart catheterization. Moreover, we will perform RNA deep sequencing on lung tissue biopsies to validate if DNA methylation signatures in circulating T cells could reflect perturbations of gene expression in lung tissues.
Detailed description
Pulmonary arterial hypertension (PAH) is characterized by remodeling of pulmonary arteries caused by an inbalance of proliferation/apoptosis rate within the vascular wall. This pathological phenotype seems to be triggered by different environmental stress and injury events such as increased inflammation, DNA damage, and epigenetic deregulation. Many immune cells are increased in PAH, such as T and B lymphocytes. Remarkably, T cells are essential players of adaptive immunity and may be relevant initiators (initial hit) of vascular remodelling. We will perform the first multi-omics study to: 1) investigate DNA methylome of circulating T cells isolated from peripheral blood of PAH patients, 2) detect transcriptomic profiles of lung tissues, 3) to assess if DNA methylation of distinct genomic regions in circulating T cells could reflect modifications of lung gene expression programs.
Interventions
None listed
Sponsors
University of Campania Luigi Vanvitelli
Study design
Observational model
CASE_CONTROL
Time perspective
CROSS_SECTIONAL
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Inclusion criteria
* Newly diagnosed patients with World Health Organization (WHO) Group I PAH. * ≥ 18 years * Documentation of the following hemodynamic parameters by right heart catheterization, performed at time of study enrolment: * Mean pulmonary arterial pressure (mPAP) \> 25 mmHg at rest or mPAP \> 30 mm Hg with exercise. * Pulmonary arterial wedge pressure (PAWP) ≤ 15 mm Hg. * Pulmonary vascular resistance (PVR) ≥ 240 dynes.sec.cm-5 (e.g., ≥ 3.0 Wood units)
Exclusion criteria
* Patients who meet the criteria for inclusion into WHO Groups II, III, IV or V. * Do not meet the required hemodynamic criteria for entry into the study. * Patients with known history of cancer, malignancy disorders, active infections, and chronic or immune-mediated diseases.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Identification of differentially methylated regions in CD04 and CD08 T cells | 3 Months | Reduced Representation Bisulfite Sequencing |
| Identification of differentially expressed genes in lung tissue biopsies | 5 Months | Chip Microarray |
| Bioinformatic analysis | 8 Months | — |
Countries
Italy
Outcome results
None listed