Endothelial Microparticles in Systemic Sclerosis Pulmonary Hypertension

Study Overview
=================
Brief Summary
-----------------
Systemic sclerosis (SSc, also known as scleroderma) is a disease characterized by fibrosis of the skin and organs, inflammation, and an abnormal endothelial cell lining inside of vessels. A common and deadly complication of SSc is pulmonary hypertension (PH), which is an abnormal elevation in the blood pressure within the lung blood vessels. Early identification and treatment of PH is important in SSc, and no clinical factors can predict which patients will develop PH with acceptable accuracy. A potential marker of PH in SSc is the presence of increased amounts of endothelial microparticles (EMPs), which are substances circulating in the blood that were released from damaged vessel wall endothelial lining. A main goal of this study is to investigate if there is a difference in EMP levels between SSc patients with and without PH. The investigators will also use human endothelial cells in a lab environment to test whether these EMPs isolated from SSc patients are actually causing damage to the vessel lining. Lastly, the investigators will investigate the potential benefit of a medication used after transplant, mycophenolate mofetil (MMF). This will be done by causing damage to isolated human endothelial cells and treating them with MMF. The main goal of this portion of our study is to see if EMP levels are reduced when cells are treated with MMF. Overall, the investigators anticipate the following outcomes of this study: 1) use EMP levels to differentiation patients with SSc who have PH from those without PH, 2) use EMPs to understand how endothelial damage occurs in SSc, and 3) use EMPs to help us develop new treatments for patients with vascular diseases.

Official Title
-----------------
Endothelial Mircroparticles as a Biomarker of Pulmonary Hypertension in Systemic Sclerosis

Conditions
-----------------
Systemic Sclerosis, Pulmonary Hypertension, Scleroderma

Intervention / Treatment
-----------------
* Other: No intervention given


Participation Criteria
=================
Eligibility Criteria
-----------------
For systemic sclerosis subjects: Inclusion Criteria: Age >18 years Meet American College of Rheumatology criteria for systemic sclerosis Exclusion Criteria: Chronic kidney disease (estimated creatinine clearance <50mL/min) Uncontrolled hypertension (diastolic blood pressure>120mmHg) Acute coronary syndrome within the past 6 months Chronic obstructive pulmonary disease Diabetes mellitus Hemolytic anemia Active tobacco abuse For healthy control subjects: Inclusion Criteria: Age>18 years Age- and sex-matched to SSc patients Exclusion criteria: Coronary artery disease Uncontrolled hypertension (diastolic blood pressure>120mmHg) Chronic obstructive pulmonary disease Chronic kidney disease Diabetes mellitus Hemolytic anemia Active tobacco abuse

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Systemic sclerosis, no pulmonary hypertension<br>This group will be systemic sclerosis patients without pulmonary hypertension | Other: No intervention given<br>* There is no intervention for this study<br>|
| Systemic sclerosis/pulmonary hypertension<br>This group will be systemic sclerosis patients with pulmonary hypertension | Other: No intervention given<br>* There is no intervention for this study<br>|
| Healthy controls<br>These will be healthy age- and sex-matched controls | Other: No intervention given<br>* There is no intervention for this study<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma VE-cadherin + endothelial microparticle levels | endothelial microparticles are expressed as microparticles per microliter of plasma. This is a cross-sectional analysis, so the measurements will be performed once, on study visit 1 | Baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma PECAM+ endothelial microparticles | endothelial microparticles are expressed as microparticles per microliter of plasma. This is a cross-sectional analysis, so the measurements will be performed once, on study visit 1 | Baseline | 
| Plasma E-selectin + endothelial microparticles | endothelial microparticles are expressed as microparticles per microliter of plasma. This is a cross-sectional analysis, so the measurements will be performed once, on study visit 1 | Baseline |