British Columbia - Dr. James Dunne, University of British Columbia

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Research re: Vascular and Endothelial Function in Systemic Sclerosis

The Scleroderma Association of BC previously co-funded research to prevent dermal fibrosis. Results are reported in the European Journal of Immunology (1998.28.2619-2629).

Effective September 2002, the Scleroderma Association of BC has committed $75,000.00 to co-fund research into the pathophysiology of scleroderma under the title Vascular and Endothelial Function in Systemic Sclerosis. This research is being conducted by

Dr. James V. Dunne, M.B., F.R.C.P., Dr. Stephan van Eeden, M.D., F.R.C.P., F.C.P.(pulmonary), Ph.D., M.Med., M.B., M.B.ChB., and their assistant, Dr. Kristina Boeva, M.D.

Dr. Dunne is Clinical Director at George Pearson Hospital, Clinical Assistant Professor at the UBC Department of Medicine, and Director of the Scleroderma Clinic at St. Paul’s Hospital in Vancouver. Dr. van Eeden is an Associate Professor of Internal Medicine at UBC and St. Paul’s Hospital. Dr Boeva is a graduate of the Ivan P. Pavlov Higher Institute of Medicine in Plovdiv with specialist training in dermatology. She recently participated in research undertaken by the Division of Dermatology at UBC.

Vascular dysfunction is a major abnormality in scleroderma. It manifests itself as Raynauds Phenomenon, pulmonary artery hypertension, renal disease, and vasculopathy. The pathophysiology of the dysfunction is poorly understood. The purpose of the study is to quantify vascular function in scleroderma and answer the following questions:

1. What is the status of the micro circulation using Laser Doppler flow measurements?

Flow in the fingers of patients with SSC and others will be measured at a baseline temperature of 20 degrees C and then repeated following warm challenge at 30 degrees C and cold challenge at 10 degrees C. The studies will be repeated after the subjects have been treated with drugs known to have both endothelial dependent or independent effects using ionophoresis or by systemic dosage. The ability of these medications to promote vasodilation and abrogate vasoconstriction will be measured.

2. What is the evidence of endothelial cell injury and activation?

Blood will be drawn at Zero time and post hot and cold challenge and assayed for circulating Von Willibrand’s Factor, 1 CAMS, and circulating endothelial cells. These measures will be correlated with clinical activity measures and blood flow responses. The presence of the foregoing markers should provide evidence of vascular endothelial injury, especially micro vascular injury.

Vascular blood flow studies are already being performed at the Scleroderma Clinic at St. Paul’s Hospital. Patients will be recruited from the Clinic and give informed consent for the use of iontophoresis and to having blood drawn for endothelial and serum studies. Depending on the success of the foregoing studies, more sophisticated studies of endothelial cell function will proceed under the direction of Dr. van Eeden in his laboratory at St. Paul’s.

The foregoing studies have the potential of providing significant insights into the pathophysiology of scleroderma and improving the management not only of this condition but of other vasculopathies as well.