Human monoclonal IgG anticardiolipin antibodies induce nitric oxide synthase expression

Abstract 

Objective

Antiphospholipid antibodies are associated with increased risk of thrombosis, particularly as in antiphospholipid syndrome. This study aims to determine the acute effects of anticardiolipin antibodies on nitric oxide production and vascular function.

Methods

Ex vivo aortic rings from male Sprague Dawley rats were incubated with IgG monoclonal anticardiolipin antibody (IS4) or a non-specific IgG control. In organ baths, response to phenylephrine and acetlycholine was determined alone and with nitro-l-arginine methyl ester (l-NAME), 1400W, d-arginine, l-arginine, sodium nitroprusside and cardiolipin. In vivo antibodies were injected into anaesthetised, spontaneously breathing male Sprague Dawley rats. Haemodynamic variables and serum nitric oxide were measured. Immunohistochemistry for iNOS and eNOS was performed in kidney vessels.

Results

Phenylepherine contraction was decreased in the IS4 group compared to controls (p<0.001). l-NAME, 1400W and cardiolipin, abolished this effect. l-Arginine caused significant relaxation in the IS4 group (p=0.005). Mean arterial pressure in rats injected with IS4 was reduced compared to IgG and saline controls (p<0.001). NO in plasma increased significantly after IS4 administration (p<0.001). Immunohistochemistry showed increased iNOS expression in kidney arteries in the IS4 group, with no change in eNOS.

Conclusion

Anticardiolipin antibodies induce NO production acutely via increased expression of iNOS in both ex vivo and in vivo models.

Keywords: Anticardiolipin antibodies, Nitric oxide, Animal model