Study of Venous Endothelial Cells in Rheumatoid Arthritis
Study Details
Study Description
Brief Summary
Heart disease is the major contributor of early death in rheumatoid arthritis (RA) and is not influenced by traditional risk factors. Blood vessel dysfunction has been associated with heart disease and complications such as heart attack. The vessel dysfunction is thought to be mediated in part to inflammation. RA patients have evidence of vessel dysfunction seen on ultrasound that improves after medications are given.
The purpose of this study is to evaluate patients with controlled or uncontrolled rheumatoid arthritis to determine if there is a difference in the protein expression in the cells that line the blood vessels compared to healthy people.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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Detailed Description
The study will consist of a cross sectional analysis of venous endothelial cells in rheumatoid arthritis patients who have controlled or uncontrolled disease and healthy controls. We will collect venous endothelial cells by placing an IV in antegrade position in the forearm and a thin wire will be inserted to collect the cells from the inner lining of the vein. The cells will processed and stained for markers of endothelial function and oxidative stress including endothelial nitric oxide synthase (eNOS), phospho-eNOS, nuclear factor kappa B (NFκB), and nitrotyrosine using immunofluorescence technique. Flow mediated dilation (FMD) by ultrasound of the brachial artery on the contralateral arm will be used as an additional marker of endothelial function. A blood sample will be taken for analysis of inflammatory markers (sedimentation rate, C-reactive protein) and cytokine analysis (IL-1, IL-6, TNFa) by cytokine bead array and flow cytometry.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Uncontrolled Rheumatoid Arthritis 18-75 years old; Rheumatoid arthritis, defined by 1987 American College Rheumatology criteria; Attending clinic at Aston Center for Rheumatology or Parkland Rheumatology Clinic; Uncontrolled: Patients will be labeled as uncontrolled RA if Disease Activity Score (DAS) score is >3.2 and C-reactive protein (mg/dL) elevated above normal range. Excluding: Insulin dependent diabetes; Cardiovascular or Cerebrovascular disease (history of myocardial infarction, stroke, peripheral vascular disease); Tobacco use in the past 24 months; Uncontrolled hypertension (BP > 150/90) in the past 3 months; Uncontrolled hyperlipidemia (LDL>160) in the past 6 months; Pregnant or nursing. |
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| Controlled Rheumatoid Arthritis 18-75 years old; Rheumatoid arthritis, defined by 1987 American College Rheumatology criteria; Attending clinic at Aston Center for Rheumatology or Parkland Rheumatology Clinic; Controlled: Disease activity score (DAS) <3.2, normal C-reactive protein. Excluding: Insulin dependent diabetes; Cardiovascular or Cerebrovascular disease (history of myocardial infarction, stroke, peripheral vascular disease); Tobacco use in the past 24 months; Uncontrolled hypertension (BP > 150/90) in the past 3 months; Uncontrolled hyperlipidemia (LDL>160) in the past 6 months; Pregnant or nursing. |
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| Healthy Controls 18-75 years old. Excluding: Insulin dependent diabetes; Cardiovascular or Cerebrovascular disease (history of myocardial infarction, stroke, peripheral vascular disease); Tobacco use in the past 24 months; Uncontrolled hypertension (BP > 150/90) in the past 3 months; Uncontrolled hyperlipidemia (LDL>160) in the past 6 months; Pregnant or nursing. |
Outcome Measures
Primary Outcome Measures
- Endothelial cell protein expression by immunofluorescence microscopy of endothelial nitric oxide synthase, nitrotyrosine, nuclear factor kappa B. [Cells are immediately processed following extraction and placed in -80 degree C freezer. Cells are then analyzed by immunofluorescence microscopy in batches of subjects. Patient is followed-up 24 hours after by phone.]
Immunofluorescence microscopy of frozen endothelial cells will be processed in batches to reduce bias. Cells are assessed for individual protein expression at study entry. Repeated collection of cells will not been done.
Secondary Outcome Measures
- Serum cytokines analysis by cytometric bead array [Measured once upon enrollment into study. Patient is followed-up 24 hours after by phone.]
Interleukin-1, Interleukin-6, Tumor Necrosis Factor -alpha
- Flow mediated dilation assessed in the brachial artery by ultrasound [Measured once upon enrollment into study. Patient is followed-up 24 hours after by phone.]
Eligibility Criteria
Criteria
Inclusion Criteria:
Rheumatoid arthritis:
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Age 18-75 years
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Rheumatoid arthritis defined by 1987 American College of Rheumatology criteria
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Attending clinic at University of Texas Southwestern Aston Clinic for Rheumatology or Parkland Arthritis Clinic.
Healthy controls:
- Age 18-75 years.
Exclusion Criteria:
Rheumatoid arthritis:
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Insulin dependent diabetes
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Cardiovascular or Cerebrovascular disease
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Tobacco use in last 24 months
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Uncontrolled blood pressure
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Uncontrolled cholesterol
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Pregnant or nursing
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Prednisone greater than 10mg per day
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Stable methotrexate dose for less than 4 weeks
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Undergoing Infliximab infusions
Healthy controls:
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Insulin dependent diabetes
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Cardiovascular or Cerebrovascular disease
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Tobacco use in last 24 months
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Uncontrolled high blood pressure
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Uncontrolled cholesterol
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Pregnant or nursing
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Parkland Memorial Hospital | Dallas | Texas | United States | 75235 |
| 2 | University of Texas Southwestern | Dallas | Texas | United States | 75390 |
Sponsors and Collaborators
- University of Texas Southwestern Medical Center
- American Heart Association
- Bristol-Myers Squibb
Investigators
- Principal Investigator: Elizabeth B Solow, MD, University of Texas
- Principal Investigator: David Karp, MD, PhD, University of Texas
Study Documents (Full-Text)
None provided.More Information
Publications
- del Rincón ID, Williams K, Stern MP, Freeman GL, Escalante A. High incidence of cardiovascular events in a rheumatoid arthritis cohort not explained by traditional cardiac risk factors. Arthritis Rheum. 2001 Dec;44(12):2737-45.
- Galarraga B, Khan F, Kumar P, Pullar T, Belch JJ. C-reactive protein: the underlying cause of microvascular dysfunction in rheumatoid arthritis. Rheumatology (Oxford). 2008 Dec;47(12):1780-4. doi: 10.1093/rheumatology/ken386. Epub 2008 Oct 14.
- Gonzalez-Juanatey C, Llorca J, Sanchez-Andrade A, Garcia-Porrua C, Martin J, Gonzalez-Gay MA. Short-term adalimumab therapy improves endo-thelial function in patients with rheumatoid arthritis refractory to infliximab. Clin Exp Rheumatol. 2006 May-Jun;24(3):309-12.
- Maradit-Kremers H, Crowson CS, Nicola PJ, Ballman KV, Roger VL, Jacobsen SJ, Gabriel SE. Increased unrecognized coronary heart disease and sudden deaths in rheumatoid arthritis: a population-based cohort study. Arthritis Rheum. 2005 Feb;52(2):402-11. Review.
- Neunteufl T, Katzenschlager R, Hassan A, Klaar U, Schwarzacher S, Glogar D, Bauer P, Weidinger F. Systemic endothelial dysfunction is related to the extent and severity of coronary artery disease. Atherosclerosis. 1997 Feb 28;129(1):111-8.
- Oemar BS, Tschudi MR, Godoy N, Brovkovich V, Malinski T, Lüscher TF. Reduced endothelial nitric oxide synthase expression and production in human atherosclerosis. Circulation. 1998 Jun 30;97(25):2494-8.
- Schwartz R, Osborne-Lawrence S, Hahner L, Gibson LL, Gormley AK, Vongpatanasin W, Zhu W, Word RA, Seetharam D, Black S, Samols D, Mineo C, Shaul PW. C-reactive protein downregulates endothelial NO synthase and attenuates reendothelialization in vivo in mice. Circ Res. 2007 May 25;100(10):1452-9. Epub 2007 Apr 19.
- Vaudo G, Marchesi S, Gerli R, Allegrucci R, Giordano A, Siepi D, Pirro M, Shoenfeld Y, Schillaci G, Mannarino E. Endothelial dysfunction in young patients with rheumatoid arthritis and low disease activity. Ann Rheum Dis. 2004 Jan;63(1):31-5.
- STU 012011-034