Data Share for AHA IPA #957261 Project
Year: 2026
Type: dataset
Abstract: The overall goal of the project is to elucidate the underlying mechanisms in endothelial cells (EC) responsible for increased thrombosis in Rheumatoid Arthritis (RA). To achieve the goal, we developed a novel mouse model of arthritis-induced thrombosis and atherosclerosis, recapitulating the cardiovascular phenotypes associated with RA in humans. Using the novel mouse model and an additional human EC culture model, two Specific Aims are proposed. A loss of the terminal sialylation in IgG Fc domain is positively associated with RA disease severity, and hyposialylated IgG impairs in vivo EC functions through interaction with FcgRIIB receptor. Aim 1 will test the hypothesis that hyposialylated IgG-induced activation of endothelial FcgRIIB promotes enhanced thrombus formation in RA mice. To determine whether IgG from RA patients have direct impacts on anti-thrombotic endothelial function, Aim 2 will employ human serum samples from our pilot cohort, and it will test the hypothesis that IgG isolated from RA patients induce thrombogenic phenotypes in cultured EC and in mice. The results (as shown in the submitted datasets) demonstrated for the first time that hyposialylation of IgG likely initiates thrombotic process through interaction with endothelial FcγRIIB. Hyposialylated IgG-FcγRIIB triggers causes attenuation of nitric oxide and elevation of vWF secretion from EC. The overall knowledge gained through the project will provide a strong scientific rationale to pursue the endothelial basis for cardiovascular diseases development in RA patients.
Source: Figshare
Author: Chieko Mineo
Subfield: Rheumatology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7203675795
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