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Endothelial vasomotor dysfunction and accelerated atherosclerosis encompass the features of rheumatoid vascular dysfunction (RVD), increasing cardiovascular morbidity and mortality among rheumatoid arthritis (RA) patients. 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’ 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. These findings highlight the usefulness of nanoparticles-targeted drug-delivery system in refining rheumatoid-induced vascular dysfunction treatment and reviving gold use in RA.

Use of 3 hydroxyl-3-methylglutaryl-3-coenzyme A reductase (HMGCR) inhibitors, or statins, reduces the progress and the complications of diabetes mellitus by modifying the lipid profile. The aim of this study was to assess the association between variation in statin response and the single-nucleotide polymorphism (SNP) rs12916 C/T in the gene encoding HMGCR, a rate limiting enzyme in cholesterol synthesis and the target enzymatic reaction of statins. A total of 96 Egyptian patients with type 2 diabetic dyslipidemia were treated with atorvastatin 20 mg/day for 3 months. Total cholesterol, triglyceride, low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C) plasma concentrations were measured at baseline and at the end of the treatment period together with genetic screening for SNP rs 12916 C/T. It was found that individuals with the CC genotype showed a mean reduction in LDL-C level of about 31.57 ± 87.52 mg/dl (p=0.24), while the reduction in the CT and TT genotypes was 28.50 ± 72.74 mg/dl (P=0.04) and 26.15 ± 101.45 mg/dl (p=0.06), respectively. It is concluded that there is no significant association between this SNP rs12916 C/T and response to atorvastatin therapy in type 2 dyslipidemic diabetic Egyptian patients.

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