Effects of Enoxaparin on Intravascular Sclerostin Release in Healthy Men.

Abstract

Sclerostin (Scl) is implicated in vascular calcification and angiogenesis and localizes within vasculature. Its molecule incorporates a heparin-binding site that implies also binding to endothelial glycocalyx. We preliminary tested whether intravenous (IV) low-molecular-weight heparin enoxaparin can stimulate intravascular release of this calcification inhibitor in humans. Sixteen male volunteers were injected with a bolus of 1 mg/kg body weight of enoxaparin. After 10 minutes, plasma immunoreactive Scl levels increased uniformly by a mean of 184% versus baseline level of 0.56 ± 0.17 ng/mL ( P = .0004). Plasma Scl levels were found still elevated after 2 and 6 hours (with a median of 20.9% and 8.69%, respectively) and became normal after 24 hours. The percentage of increase (Δ) in plasma Scl after 10 minutes was directly correlated with enoxaparin dose per kg/m2 of body mass index (ρ = 0.587, P = .017) and strongly inversely correlated with the preinjection Scl levels (ρ = -0.747, P = .0008). A robust negative association between the ΔScl increase after 10 minutes and the ΔScl decrease after 2 hours versus 10 minutes was observed (ρ = -0.835, P < .0001). Complementary in vitro spiking experiment showed no effects of enoxaparin addition and whole blood incubation on plasma Scl levels when measured with the immunoassay. This study shows that enoxaparin has a stimulating effect on the intravascular release of calcification inhibitor Scl in healthy men. This novel pharmacological action of the popular anticoagulant drug seems important in cardiovascular medicine.