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CIRCULATING PROSTAGLANDIN D2 SYNTHASE (PGDS)LEVELS IN PULMONARY HYPERTENSION

Winthrop-University Hospital, Mineola, NY

PURPOSE: Eicosanoids have been linked to the control of both pulmonary artery (PA)smooth muscle function and proliferation and are important in the contol of pulmonary hypertension (PH). One such prostaglandin, prostaglandin D2 (PGD2) has been shown to be a mediator of apoptosis and in many studies is antiproliferative to smooth muscle growth. The role of PGD2S, a circulating enzyme, has not been investigated in PH. We examined the circulating levels of PGDS in 20 PH patients and 20 age and sex matched controls without PH.

METHODS: Patients were >18, non-pregnant, and did not have renal failure, systemic hypertension, diabetes mellitus and were not using nonsteroidal anti-inflammatory agents, COX-2 inhibitors, or aspirin. Five milliliters of blood was drawn by venipuncture and centrifuged at 2000 X G, and the sera frozen at -80°C for later assay. Both lipocalin and hematopoeitic forms of PGDS were assayed by enzyme linked immunoabsorbant assay. Patient characterisics including systolic PA and mean PA pressures, age, sex, therapy at the time of assay, and New York Heart Association functional class were recorded.

RESULTS: Lipocalin PGDS was found in significantly higher levels in PH patients than in controls [mean=1030 ng/ml SEM=97.6 vs. 652 ng/ml SEM=42.5; p=0.003]. No significant differences were found between male and female patients [female mean=1017 ng/ml SEM=147 vs. male means=1109 ng/ml SEM=111; p=0.672]. Correlation with PGDS levels and degree of PH as reflected by systolic PA pressure was modest [R2=0.20].

CONCLUSION: Circulating levels of PGDS are elevated in PH and correlate modestly with systolic PA pressures. No apparent differences between male and female patients with PH were noted. A larger study of PH patients is warranted.

CLINICAL IMPLICATIONS: The significance of elevated PGDS levels remains to be clarified. Whether this is a primary anomaly in PH or an attempt to defend against other primary causes of smooth muscle overgrowth remains to be defined. Inverse correlation with mean PA pressures raises the possibility of using PGDS levels as a marker of disease severity or response to therapy.

DISCLOSURE: Terence Trow, None.