Our hypothesis is that optimal treatment of the dysfunctional metabolic pathways which underlie PAH will improve pulmonary vascular function and consequences of the disease.
Diagnosis of IPAH (idiopathic pulmonary arterial hypertension), HPAH (heritable pulmonary arterial hypertension), or APAH (associated pulmonary arterial hypertension), family members of affected persons
Age 0-90, age 12-90 for skin biopsy
Other diagnosis
Age greater than 90, age less than 12 or greater than 90 for skin biopsy
None
Cohort 1 subjects will be recruited from our adult and pediatric pulmonary vascular disease clinics. Cohort 2-healthy controls will be recruited form patients families and the general public in middle Tennesssee.
Cohort
Prospective
Not listed
Ratio of sex hormone metabolites
The primary outcome measure is the ratio of 2-hydroxyestrogens to 16-hydroxyestrogens among patients compared to both controls and at risk but well subjects.
Evaluation of insulin resistance in pulmonary arterial hypertension patients/Clinical trial of Metformin in Pulmonary Arterial Hypertension
We will assess various measures of insulin resistance among patients, compared to healthy control subjects as well as at risk but well subjects. The primary measure will be assessed using the glucose clamp technique to quantify insulin secretion and resistance.
Mechanism, safety, and efficacy of ACE-2 (Angiotensin Converting Enzyme 2) in the treatment of PAH.
We will assess the safety and efficacy of ACE-2 for the treatment of established PAH. The primary objective of the study is to determine safety of rhACE2 when administered as a single dose or multiple doses intravenously to subjects with PAH receiving background PAH-specific therapy.
Clinical Trial of Metformin in Pulmonary Arterial Hypertension
Specific Aim 1. To test the hypothesis that metformin will ameliorate oxidant stress in pulmonary arterial hypertension Primary safety endpoint: absence of lactic acidosis, withdrawal from the study if attributed to metformin Primary efficacy endpoint: change in urinary and plasma oxidant stress measures (F2 isoprostanes and metabolites, isofurans, and nitrotyrosine) Specific Aim 2. To test the hypothesis that metformin will decrease myocardial lipid content, increase oxidative metabolism and decrease glucose uptake. Primary Endpoints: change in myocardial percent triglycerides (%TGs), kmono/RPP of C11 acetate, and uptake of FDG before and after metformin.
Mechanism, safety, and efficacy of ACE-2 in the treatment of PAH.
The secondary objective of the study is to evaluate changes in biomarkers of disease (BNP, AngII/Ang (1-7, serum soluble IDH, serum NO, cardiac troponin I, SOD2 activity, urine isoprostanes and isofuranes) in subjects with PAH receiving rhACE2. We will also evaluate changes in pulmonary and systemic hemodynamics and echocardiographic markers of right heart function in patients receiving rhACE2.
Clinical Trial of Metformin in Pulmonary Arterial Hypertension
Specific Aim 1. To test the hypothesis that metformin will ameliorate oxidant stress in pulmonary arterial hypertension Secondary Endpoints: lung cellular proliferation as measured by FDG avidity, change in the markers of insulin resistance and sensitivity, BMPR2 expression in peripheral blood mononuclear cells, and change in glucose and lipid metabolites. Specific Aim 2. To test the hypothesis that metformin will decrease myocardial lipid content, increase oxidative metabolism and decrease glucose uptake. Secondary Endpoints: change in RVEF, RV mass index, insulin resistance and sensitivity indices, glucose and lipid metabolites, and six-minute walk distance (6MWD)
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