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Methotrexate, among DMARDs, effectively reduces cardiovascular events, but its non-selectivity together with its pharmacokinetic variability often limit drug adherence and contribute to its potential toxicity. Thus, methotrexate was conjugated to gold nanoparticles (MTX\/AuNPs) and its effect on RVD in rats\u2019 adjuvant-induced arthritis was evaluated. A comparative study between MTX\/AuNPs, free MTX, and AuNPs treatments on joint inflammation, vascular reactivity and architecture, smooth muscle phenotype, systemic inflammation, and atherogenic profile was done. Since MTX\/AuNPs effect was superior, it appears that conjugation of MTX to AuNPs demonstrated a synergistic action. MTX immunomodulatory action combined with AuNPs anti-atherogenic potential yielded prompt control of whole features of RVD. 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