ENDOTHELIN-1 IMMUNOREACTIVITY IN PLASMA IS ELEVATED IN HIV-1-INFECTEDPATIENTS WITH RETINAL MICROANGIOPATHIC SYNDROME

Endothelin-1 is a recently identified cytokine with potent vasoconstri ctor activity which is associated with various diseases involving bloo d vessels. HIV-1 related retinal microangiopathic syndrome is a freque nt finding in patients with AIDS or AIDS-related complex, presenting p redominantly with retinal cotton-wool spots. We investigated 55 HIV-1 infected patients by ophthalmoscopy and for endothelin-1 immunoreactiv ity in plasma and an additional 76 HIV-1 infected patients only for en dothelin-1 levels. For reference values 13 age-matched healthy subject s were studied. In 18 of 55 patients (33%) investigated ophthalmoscopi cally we found evidence of microangiopathic syndrome. Overall, the mea n endothelin-1 immunoreactivity in plasma of HIV-1 infected patients w as significantly elevated as compared to controls (4.28 +/- 3.62 versu s 2.72 +/- 0.67 fmol/ml, P < 0.0001). HIV-1 infected patients with ret inal microangiopathic syndrome had significantly higher plasma levels of endothelin-1 immunoreactivity (4.59 +/- 1.38 fmol/ ml) compared to HIV-1 infected patients without microangiopathic syndrome (3.18 +/- 1. 64 fmol/ml, P = 0.003). Correlation analysis revealed that endothelin- 1 immunoreactivity in plasma had no significant association with disea se progression, CD4 cell count, beta2-microglobulin, neopterin, or age . Endothelin-1 immunoreactivity in plasma was correlated exclusively w ith retinal microangiopathic syndrome in one or both eyes (r = 0.45, P = 0.0006) and with the number of cotton-wool spots (r = 0.50, P = 0.0 001). In conlusion, HIV-1 related retinal microangiopathic syndrome is associated with elevated plasma levels of endothelin-1. By virtue of its potent vasoconstrictor activity endothelin-1 may be involved in th e pathogenesis of HIV-1 related vascular disease.