Karen Lyons, Ph.D.
Orthopaedic Hospital Research Center at UCLA

"Role of CTGF in Vascular Remodeling in Scleroderma"

Established Investigator

Microvascular abnormalities are the earliest and most common manifestations of Scleroderma (Systemic sclerosis, SSc).

The mechanisms underlying vascular alterations in SSc patients are entirely unknown, but several lines of evidence point to a central role for Connective Tissue Growth Factor (CTGF). CTGF stimulates extracellular matrix (ECM) production, a process that is accelerated in SSc. Moreover, CTGF has recently been identified as a genetic risk factor for SSc. CTGF is highly expressed in blood vessels, but the role of CTGF in vessels is unclear, as it appears to have the ability to stimulate or inhibit blood vessel formation, depending on the type of assay. Ongoing studies have revealed that CTGF is essential for capillary maintenance during development, raising the possibility that blood vessels are a key target of the damage caused by elevated levels of CTGF in SSc patients. Understanding the role of CTGF in normal capillary maintenance will yield key insights into the role CTGF plays in SSc. Clinical trials involving inhibition of CTGF activity for the treatment of fibrotic conditions such as SSc are currently ongoing. It is therefore essential to determine whether there will vascular
damage associated with long-term CTGF inhibition in adults.