PP.07.13: NETRIN-1 LEVELS ARE REDUCED IN HEALTHY SUBJECTS IN RESPONSE TO TREATMENT WITH ASPIRIN. (June 2015) - Layne, K.
Abstract : Objective: Pro-inflammatory stimuli and pro-atherogenic factors are known to reduce the level of endothelial-derived netrin-1, a secreted laminin-like protein that attenuates recruitment of circulating monocytes within atherosclerotic plaques. This study investigated the effect of aspirin, routinely used for the prevention of cardiovascular disease, on serum netrin-1 levels in healthy subjects. Design and method: Serum netrin-1 was measured using an enzyme-linked immunosorbent assay (ELISA) in samples collected from 60 subjects before and after 28 days of treatment with 300 mg aspirin daily. ELISAs were performed to assess serum levels of intercellular adhesion molecule-1 (ICAM-1), E-selectin, and urinary 11-dehdyro-thromboxane B2 levels (TXB2). Serum creatinine and salicylate levels were measured using the creatininase enzymatic method on a Roche C8000 analyser and a Cobas Fara automated analyser (Roche) respectively. Creatinine clearance was calculated using the Cockcroft-Gault equation. The Research Ethics Committee approved this study and subjects signed consent forms. Results: Serum netrin-1 levels were reduced following aspirin treatment (66.06 ± 22.98pg/ml versus 79.79 ± 34.91pg/ml at baseline; p = 0.0022). There was a linear association between the percentage change in netrin-1 and level of serum salicylate (r2 = 0.413, p = 0.0013). TXB2 levels fell in all subjects post-treatment, confirming adherence to treatment (32.99 ± 18.35ng/mmol creatinine versus 143.7 ± 54.25ng/mmol creatinine at baseline; p < 0.0001). Serum ICAM-1 and E-selectin levels were not modified by treatment. Creatinine clearance decreased following aspirin (103.2 ± 26.13 ml/min versus 110.5 ± 26.95 ml/min at baseline; p = 0.0011). Conclusions: This study demonstrates that serum netrin-1 is reduced following treatment with aspirin. The TXB2 measurements show effective platelet inhibition in the whole population. We observed no change in ICAM-1 or E-selectin levels suggestive of an effect on the vascular endothelial function. Netrin-1 is a known biomarker of renal impairment. We propose that the reduction in netrin-1 is secondary to drug-induced renal dysfunction, as evidenced by a decrease in creatinine clearance.