Background/Purpose

Cell-derived microparticles (MPs) could be considered biomarkers of cell damage and activation and they are thought to have a role in cardiovascular (CV) and inflammatory diseases. Since Rheumatoid Arthritis (RA) is characterized by immune and endothelial activation, the main aim of this study was to evaluate MP counts in RA patients.

Methods

MPs were analyzed by flow cytometry following a total-labelling procedure in platelet-poor plasma from 33 healthy controls (HC), 72 individuals with marked CV risk (CVR: diabetes, n=24; dyslipidemia, n=27; and hypertension, n=41) and 114 RA patients (61.4% RF, 61.4% αCCP, DAS28: 3.61(1.97), 42.1% erosive disease). Different subsets were identified by their surface markers: platelet- (CD41⁺, PMPs), endothelial- (CD146⁺, EMPs), granulocyte- (CD66⁺, GMPs), monocyte- (CD14⁺, MoMPs) and Tang-derived (CD3⁺CD31⁺, Tang-MPs). TNFα serum levels were quantified by ELISA. In vitro assays on Matrigel with HMEC-I cells were performed to assess the effect of MPs on endothelial functionality. Clinical and immunological parameters as well as traditional CV risk factors (diabetes, hypertension, dyslipidemia, obesity and smoking) were registered from clinical records and all data were analyzed by Principal Component Analysis (PCA).

Results

Total MPs count was increased in RA compared to both HC (p<0.0001) and CVR (p=0.0009) and was positively correlated with traditional CV risk factors (BMI, TC/HDL ratio, triglycerides and number of risk factors). Additionally, specific MPs subsets were increased in RA (EMPs p<0.0001, GMPs p<0.0001, Tang-MPs p=0.006 and MoMPs p=0.028). Clinical data were integrated with PCA and 4 components were identified. Notably, different MP subsets correlated with different components (table 1), thereby involving specific disease features in MPs profile. Interestingly, TNFα correlated with Tang-MPs in RA after adjusting by traditional risk factors (r=0.218, p=0.036). Finally, MPs from RA patients were able to impair endothelial cell functionality (measure as tube formation and number of branching points) in vitro in a dose-dependent manner, linked to an upregulation of endothelial activation markers (CD62E, CD144 and VEGFR2). This effect appeared even within the physiological range and it was not present with HC or CVR MPs.

Conclusion

MPs analysis in RA patients revealed an increased damage in several cell types. Circulating MPs from RA patients displayed a unique quantitative and qualitative profile as the result of both disease-specific and traditional CV risk factors. These differences are independent of comorbidities. Accordingly, this MP profile could underlie the detrimental effects on endothelial cells in vitro, thus supporting their role as biomarkers of endothelial damage and vascular repair failure.

Table 1: PCA components
	Rheumatic-related	Traditional CV-related	Duration-related	Inflammation-related
Total MPs	0.110 0.345	0.381 0.0007 ***	0.065 0.576	0.022 0.848
PMPs	0.018 0.881	0.078 0.506	0.096 0.410	0.050 0.668
EMPs	-0.016 0.894	0.017 0.884	0.302 0.005 **	-0.091 0.446
GMPs	0.277 0.022 *	-0.004 0.975	0.042 0.721	0.050 0.667
Tang-MPs	0.299 0.003 **	-0.035 0.768	-0.028 0.816	0.134 0.262
MoMPs	-0.098 0.414	-0.111 0.356	-0.153 0.202	0.114 0.343

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/a-distinct-profile-of-circulating-microparticles-is-associated-with-disease-features-in-rheumatoid-arthritis-patients-and-impairs-endothelial-functionality-in-vitro/