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

Abstract

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.

The effect of captopril on lipopolysaccharide-induced lung inflammation

“…Angiotensin converting enzyme inhibitors play a key role in pulmonary inflammatory diseases and severe acute respiratory syndrome and possibly contribute to pulmonary disease. 41 In previous studies, it has been claimed that presence of thiol groups in captopril results in neutralization of free radicals, 42 and anti-inflammatory effects 43 which reduce oxidative stress and inflammatory responses.…”

Silencing of SAA1 inhibits palmitate- or high-fat diet induced insulin resistance through suppression of the NF-κB pathway

“…SAA, which is predominantly found in the bloodstream at 0.1 μM, is an acute-phase protein with apolipoprotein properties that has been implicated in the development of a number of pathological conditions, including type 2 diabetes mellitus (Baranova et al 2005; Lakota et al 2018). SAA, a classical, acute-phase protein and a product of hepatocytes, could potentially respond to infection, injury and inflammation and also has the ability to regulate toll-like receptor 4 (TIR4) which is associated with obesity-induced insulin resistance (Odhah et al 2018; Sandri et al 2008; Shi et al 2006; Tannock et al 2018).…”