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

Atherosclerosis (AS) is one of themost prevalent causes of death around theworld. Since there
are different types of risk factors, different types ofmedications focus on preventing atheromas and plaques
from establishing or on preventing established plaques from growing.
Objectives. The aim of this studywas 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 (20mg/kg/day), Group 4 received atRA (5mg/kg/day, orally), and Group 5
received both drugs. Allmedicationswere 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 differencewas 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). Themaximum vessel wall and intima thick-
ness 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).
Conclusions. 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