Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
JCR Impact Factor (IF) – 1.736
5-Year Impact Factor – 2.135
Index Copernicus  – 168.52
MEiN – 70 pts

ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
Periodicity – monthly

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Advances in Clinical and Experimental Medicine

2018, vol. 27, nr 12, December, p. 1631–1636

doi: 10.17219/acem/74552

Publication type: original article

Language: English

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All-trans retinoic acid effectively reduces atheroma plaque size in a rabbit model of high-fat-induced atherosclerosis

Leila Zarei1,A,B,D,F, Mehran Bahrami2,B,C,D, Negin Farhad2,B,D, Seyyed Meysam Abtahi Froushani3,B,D, Ata Abbasi4,A,C,D,E,F

1 Solid Tumor Research Center, Urmia University of Medical Sciences, Iran

2 Student Research Committee, Urmia University of Medical Sciences, Iran

3 Department of Microbiology, Veterinary Faculty, Urmia University, Iran

4 Department of Pathology, Faculty of Medicine, Urmia University of Medical Sciences, Iran

Abstract

Background. Atherosclerosis (AS) is one of the most prevalent causes of death around the world. Since there are different types of risk factors, different types of medications focus on preventing atheromas and plaques from establishing or on preventing established plaques from growing.
Objectives. The aim of this study was to evaluate the effect of all-trans retinoic acid (atRA) on AS in a rabbit model of fat-induced AS.
Material and Methods. Atherosclerosis was induced by a high-fat diet (HFD) for 75 days. Thirty rabbits were randomly divided into 5 groups. Group 1 was the negative control group and received a normal diet. The animals in the other groups were fed a HFD. Group 2 (the AS positive control group) received no drugs, Group 3 received atorvastatin orally (20 mg/kg/day), Group 4 received atRA (5 mg/kg/day, orally), and Group 5 received both drugs. All medications were started on day 45 and continued until the end of the study. Fasting blood samples were obtained for lipid profile evaluation. The aorta sections were evaluated for maximum wall and intima thickness.
Results. Oral administration of atRA, atorvastatin or their combination significantly improved serum lipid profile (p < 0.001). Atorvastatin and atRA significantly decreased serum total cholesterol and LDL-cholesterol levels in HFD (p < 0.001). No difference was found in serum HDL-cholesterol levels among the studied groups. The HFD group (Group 2 – positive control) showed significant intima irregularities with fat deposition and foamy macrophage accumulation (atheroma). Administration of atRA and atorvastatin significantly decreased the size of atherosclerotic plaques (intima thickness). The maximum vessel wall and intima thickness were significantly decreased after atRA and atorvastatin administration (p < 0.001). No difference was found between atRA and atorvastatin effectiveness, but combination therapy significantly decreased AS size in comparison to using either of the drugs alone (p < 0.001).
Conclusion. In reducing AS plaque size, atRA is as effective as atorvastatin. Additionally, the combination therapy of atRA and atorvastatin decreased AS size much more effectively, showing their synergistic effect. atRA can also improve the serum lipid profile.

Key words

atherosclerosis, high fat diet, all-trans retinoic acid

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