Simvastatin Nano-formulation Exhibited Protective Effect in Cellular Model of Atherosclerosis via Inhibition of Osteopontin Expression
| Author | Asma Khawer | en |
| Author | Talat Roome | en |
| Author | Uzma Zaman | en |
| Author | Shazmeen Aslam | en |
| Author | Hafiz Syed Imran ul Haq | en |
| Author | Midhat Batool Zaidi | en |
| Author | Muhammad Raza Shah | en |
| Author | Muhammad Kashif | en |
| Orcid | Asma Khawer [0009-0005-3868-2988] | en |
| Orcid | Talat Roome [0009-0006-7762-0381] | en |
| Orcid | Uzma Zaman [0000-0002-8623-155X] | en |
| Orcid | Shazmeen Aslam [0000-0002-5060-0667] | en |
| Orcid | Hafiz Syed Imran ul Haq [0009-0008-7536-2256] | en |
| Orcid | Midhat Batool Zaidi [0000-0001-5800-3157] | en |
| Orcid | Muhammad Raza Shah [0000-0003-4978-3627] | en |
| Orcid | Muhammad Kashif [0000-0002-4586-5302] | en |
| Issued Date | 2025-12-31 | en |
| Abstract | Background: Atherosclerosis is among the primary causes of mortality globally due to its ability to induce cardiovascular and cerebrovascular events. Osteopontin (OPN) is a pro-inflammatory cytokine that plays an important role in the development of atherosclerosis. Simvastatin, a lipid-lowering drug belonging to the statin class, is known to decrease plasma OPN levels. However, its unfavorable pharmacokinetic profile, characterized by extensive first-pass metabolism leading to poor bioavailability, has restricted its clinical use. Objectives: The present study aimed to assess the efficacy of a nano-formulation of simvastatin [folate-conjugated simvastatin silver (Ag) nano-formulation] in a cellular model of atherosclerosis. Methods: This interventional study was performed on adventitial fibroblasts obtained from rat aorta. The cell viability of aldosterone-stimulated adventitial fibroblasts was evaluated in the presence of simvastatin and its nano-formulation using the MTT (3-[4,5-dimethylthiazole-2-yl]2,5-diphenyltetrazolium bromide) assay and microscopic observation. The expression and quantification of OPN were performed using qPCR and ELISA, respectively. The presence of reactive oxygen species (ROS) was estimated using a fluorescent probe, dihydroethidine (DHE). Variation among data was computed using one-way ANOVA followed by post hoc analysis (Bonferroni post hoc test) using SPSS software (version 19.0, SPSS Inc., Chicago, IL). Results: The nano-formulation of simvastatin was most effective (P < 0.05) in retaining the viability of fibroblasts (300% at 10 μM, P < 0.001), which was significantly decreased (50% at 10 μM, P < 0.001) after aldosterone treatment. Additionally, the formulation prevented the aldosterone-induced increase in OPN expression in fibroblasts. However, ROS levels remained unaltered in all groups. Conclusions: The nano-formulation of simvastatin demonstrated a protective effect in a cellular model of atherosclerosis, likely due to its ability to prevent the increase in aldosterone-induced OPN expression. Assuming a favorable pharmacokinetic profile, owing to its reduced size and folate conjugation, the formulation warrants further investigation in the anti-atherosclerosis drug discovery program. | en |
| DOI | https://doi.org/10.5812/icrj-160072 | en |
| Keyword | Atherosclerosis | en |
| Keyword | Osteopontin | en |
| Keyword | Adventitial Fibroblasts | en |
| Keyword | Simvastatin | en |
| Keyword | Nano-formulation | en |
| Publisher | Brieflands | en |
| Title | Simvastatin Nano-formulation Exhibited Protective Effect in Cellular Model of Atherosclerosis via Inhibition of Osteopontin Expression | en |
| Type | Research Article | en |