Analysis of Drug Effects on Primary Human Coronary Artery Endothelial Cells Activated by Serum Amyloid A

Abstract EN

Background.

RA patients have a higher incidence of cardiovascular diseases compared to the general population.

Serum amyloid A (SAA) is an acute-phase protein, upregulated in sera of RA patients.

Aim.

To determine the effects of medications on SAA-stimulated human coronary artery endothelial cells (HCAEC).

Methods.

HCAEC were preincubated for 2 h with medications from sterile ampules (dexamethasone, methotrexate, certolizumab pegol, and etanercept), dissolved in medium (captopril) or DMSO (etoricoxib, rosiglitazone, meloxicam, fluvastatin, and diclofenac).

Human recombinant apo-SAA was used to stimulate HCAEC at a final 1000 nM concentration for 24 hours.

IL-6, IL-8, sVCAM-1, and PAI-1 were measured by ELISA.

The number of viable cells was determined colorimetrically.

Results.

SAA-stimulated levels of released IL-6, IL-8, and sVCAM-1 from HCAEC were significantly attenuated by methotrexate, fluvastatin, and etoricoxib.

Both certolizumab pegol and etanercept significantly decreased PAI-1 by an average of 43%.

Rosiglitazone significantly inhibited sVCAM-1 by 58%.

Conclusion.

We observed marked influence of fluvastatin on lowering cytokine production in SAA-activated HCAEC.

Methotrexate showed strong beneficial effects for lowering released Il-6, IL-8, and sVCAM-1.

Interesting duality was observed for NSAIDs, with meloxicam exhibiting opposite-trend effects from diclofenac and etoricoxib.

This represents unique insight into specific responsiveness of inflammatory-driven HCAEC relevant to atherosclerosis.