Detrimental Effect of Plasma From Patients With Severe Aortic Stenosis on Valvular Endothelial Cells: Role of Proinflammatory Cytokines and Factor Xa
Abstract
BACKGROUND: The role of plasma and its components in the progression of aortic stenosis (AS) remains insufficiently investigated. This study aimed to assess whether plasma from patients with AS induces oxidative stress and contributes to valvular endothelial cells (VECs) dysfunction.
METHODS: Human plasma samples were obtained from patients with severe AS (AS+, n=110), patients with cardiovascular risk factors without AS (n=30), and healthy individuals (n=15). Plasma levels of proinflammatory cytokines (IL [interleukin]-1β, IL-6, TNF [tumor necrosis factor]-α, and factor Xa [FXa]) were measured. Porcine aortic VECs were then incubated with plasma (10%, 24 hours). Oxidative stress levels were assessed using dihydroethidium staining, NO formation with 4-amino-5-methylamino-2',7'-difluororescein diacetate, mRNA expression by quantitative reverse transcription-polymerase chain reaction, and protein expression levels by Western blot analyses. Platelets and monocytes adhesion as well as thrombin generation were determined. Different pharmacological inhibitors were used to explore the underlying pathways.
RESULTS: Plasma from patients with AS+ exhibited elevated levels of IL-1β, IL-6, TNF-α, and FXa activity. Incubation of VECs with AS+ plasma induced a pro-oxidant response mediated by proinflammatory cytokines, the angiotensin system-SGLT2 (sodium-glucose transport protein 2) pathway, and FXa. AS+ plasma also triggered VEC dysfunction, inflammation, monocytes and platelets…
How strong is the evidence?
Evidence Hub reads this as a case-control, done in people. Its evidence level is 4 of 5 (Low · observational). Observational designs can show an association but not prove cause. Reported size: 110 participants or records.
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