Angiotensin Converting Enzyme (ACE2), Brain, Gut Dysbiosis in Pulmonary Hypertension

Study Overview
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Brief Summary
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Pulmonary arterial hypertension (PAH) is fatal with right heart failure due to raised pulmonary vascular pressure. Gut dysbiosis was identified in animals with pulmonary hypertension. Deidentified human samples will be tested for gut dysbiosis in PAH, circulating bacterial metabolites and markers of inflammation and gut leakiness. The gut microbiome and circulating metabolites, markers of inflammation and gut leakiness of PAH patients and healthy subjects will be compared in deidentified fecal samples and blood.

Detailed Description
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Stool samples will be collected from people with no, mild-moderate or severe pulmonary arterial hypertension. Bacterial DNA will be extracted from the feces and sequenced by whole genome sequencing (shotgun sequencing). The DNA sequences will be used to identify the bacteria present in the feces, and to model the functions of the gut microbial community in each of the three groups. This will test for gut dysbiosis in pulmonary arterial hypertensive patients compared to healthy subjects. Gut dysbiosis is a condition where the gut bacterial communities are unbalanced and has been implicated in disease processes. In subjects recruited in the USA, blood samples will be tested for markers of gut leakiness and inflammation as well as gut bacterial metabolites found in the circulation.

Official Title
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Angiotensin Converting Enzyme (ACE2), Brain, Gut Dysbiosis in Pulmonary Hypertension

Conditions
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Pulmonary Arterial Hypertension

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: severe, mild-moderate or no pulmonary arterial hypertensive subjects Exclusion Criteria: Patients with pulmonary hypertension due to left heart disease, lung diseases and / or hypoxia, chronic thromboembolic pulmonary hypertension, and pulmonary hypertension with unclear multifactorial mechanisms.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Severe pulmonary arterial hypertension.<br>This cohort will consist of patients with severe pulmonary arterial hypertension. This is defined as mean pulmonary arterial pressure 25 mm Hg or greater and pulmonary artery occlusion pressure 15 mmHg or less measured by right cardiac catheterization and a clinical diagnosis of severe disease. Participants will be without signs of left heart disease, lung disease and or hypoxia, chronic thromboembolic pulmonary hypertension or pulmonary hypertension of unclear multifactorial mechanisms. This is an observational study with no interventions. | |
| Mild-moderate pulmonary arterial hypertension<br>This cohort will consist of patients with mild-moderate pulmonary arterial hypertension. This is defined as mean pulmonary arterial pressure 25 mm Hg or greater and pulmonary artery occlusion pressure 15 mmHg or less measured by right cardiac catheterization and a clinical diagnosis of mild-moderate disease. Participants will be without signs of left heart disease, lung disease and or hypoxia, chronic thromboembolic pulmonary hypertension or pulmonary hypertension of unclear multifactorial mechanisms. This is an observational study with no interventions. | |
| Reference subjects without pulmonary hypertension<br>Reference subjects will be healthy people, age- and sex-matched to the other two cohorts, who have no pulmonary artery hypertension. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gut-microbial dysbiosis | Identification of fecal microbiota and the function of the gut microbial community | 3 weeks |