Background/Purpose: Bone marrow derived stem cells, endothelial progenitor cells (EPCs), protect against atherosclerotic vascular damage by overcoming endothelial damage. However, EPCs are depleted in RA and contribute to the enhanced cardiovascular (CV) risk. Therapeutic potential of augmenting EPCs to treat the heightened CV risk of RA has not yet been exploited. We aimed to investigate the effect of rosuvastatin on EPCs population, endothelial dysfunction, nitrite, adhesion molecules and on markers of inflammation in RA.

Methods:

50 RA patients were randomized to receive 24 weeks of treatment with rosuvastatin (10mg/day, n=25) or placebo (n=25) as an adjunct to existing stable antirheumatic drugs. EPCs (CD34+/CD133+) were quantified by Flow Cytometry. Flow mediated dilatation (FMD) was assessed by AngiodefenderTM (Everest Genomic Ann Arbor, United States). Inflammatory measures included DAS28, CRP, ESR and Pro-inflammatory cytokines (TNF-α, IL-6 and IL-1) were measured at baseline and after treatment. Estimation of serum nitrite, Lipids, and adhesion molecules (ICAM-1 and VCAM-1) was done at baseline and after treatment.

Results:

At baseline, inflammatory measures, pro-inflammatory cytokines, adhesion molecules and nitrite levels were elevated and EPCs and endothelial function were impaired among both groups. At 24 wks: DAS28, ESR, CRP, TNF-α and IL-6 improved significantly (p<0.05) in rosuvastatin group. Concentration of serum nitrite (p=0.02) and ICAM-1 (p=0.01) was significantly lower in the rosuvastatin group compared with placebo. EPCs increased significantly from (CD34⁺/CD133⁺, 0.01±0.001 to 0.035±0.001, p<0.01) after treatment with rosuvastatin as compared with placebo and after 24 wks percentage change in EPCs was 71.4% and 22.2% in the rosuvastatin and placebo groups respectively (Fig.1). After treatment with rosuvastatin there was significant improvement in FMD (p<0.01) as compared to placebo. Rosuvastatin exerted positive effect on lipid spectrum by signicantly increasing HDL cholesterol levels (p=0.01) and decreasing LDL cholesterol (p=0.02). Significant inverse correlation was observed between EPCs and CRP (r=-0.44, p=0.02), TNF-α (r=-0.42, p=0.03), ICAM-1(r=-0.45, p=0.03) and FMD(r=-0.47, p=0.01) after treatment with rosuvastatin.

 

Conclusion: First study to show that rosuvastatin augments EPCs population in RA mediated by lowering the levels of cytokines, especially IL-6 and TNF-α, which downregulates adhesion molecule, CRP and nitric oxide production. This defines a novel mechanism of rosuvastatin treatment in patients with RA: the augmentation of EPCs with improvement in inflammatory disease activity and endothelial dysfunction. The augmentation of EPCs by rosuvastatin represents a fascinating new approach for the management of RA.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/stem-cell-augmentation-for-cardiovascular-risk-in-rheumatoid-arthritis/