Endothelial cell dysfunction in systemic vasculitis: new developments and therapeutic prospects

The role of the endothelium as an active player rather than a passive victim of inflammation has received considerable interest in atherosclerosis, but less so in systemic vasculitis (SV). However, the accumulating multi-organ damage seen in SV probably includes the endothelium. Assessment of endothelial function is now a standard clinical research tool in cardio-vascular departments. The exciting insights provided by their application to SV, in both primary disease and connective tissue diseases (CTD), is reviewed here.

Diffuse endothelial cell dysfunction (ECD) documented by several techniques occurs commonly in adult and childhood SV. Similar ECD is also seen in CTD. The mechanisms probably relate to inflammatory cytokines such as TNF. The particular role of vasculitic, as opposed to synovial or internal organ inflammation, may be release of secondary mediators directly into the blood stream- whence they can reach distant endothelial beds to induce this diffuse ECD.

Endothelial injury is the first step in atherosclerosis, where peripheral abnormalities correlate with coronary artery responses. The diffuse ECD in CTD suggests that vascular inflammation may initiate the accelerated CVS disease there. The new findings of similar ECD in primary SV predicts enhanced atherosclerosis here too. In Kawasaki syndrome, persistent late ECD correlates with abnormal coronary responses. In adult SV, initial data also suggests increased subclinical atherosclerosis. The role of endothelial function in the clinical outcome of SV deserves more attention. Research to pinpoint the mechanisms of ECD should lead to more specific therapies that may ameliorate the continuing late morbidity and mortality of SV.