Abstract
The effect of proteasome inhibitors on atherosclerosis is known to vary depending on the atherosclerosis stage. Previous studies have shown that the highest proteasome expression in atherosclerotic lesions is at the progression stage. Adhesion molecules play a role in the progression stage of atherosclerosis, but no studies have analyzed the effect of proteasome inhibitors on the expression of adhesion molecules at this stage. This experimental study aimed to analyze the effect of a proteasome inhibitor, namely bortezomib, on the vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule1 (ICAM-1) expressions in blood vessels of rat model of atherosclerosis at the progression stage. This study used 18 male Wistar rats divided into three groups, i.e. group I that is the control group given standard feed, group II induced by atherosclerosis, and group III induced by atherosclerosis and given bortezomib. Atherosclerosis induction was performed using vitamin D3 (700,000 IU/kg) orally by gastric intubation on the 1st day and atherogenic feed given for four days. Bortezomib 50 µg/kgBW/day was administered intra-peritoneally. The expression of VCAM-1 and ICAM-1 molecules was measured using immunohistochemistry and analyzed quantitatively using Adobe Photoshop software. The statistical test showed differences in VCAM-1 expression between atherosclerosis + Bortezomib group and atherosclerosis group, but there were no differences in the expression of ICAM-1 and atherosclerotic lesions between the groups. Administration of bortezomib 50μg/kg for four days in progressive atherosclerosis model rats can inhibit VCAM-1 expression, although it does not affect ICAM-1 expression and cannot inhibit atherosclerotic lesion formation.
Highlights
Cardiovascular diseases (CDVs), consisting of coronary heart disease and cerebrovascular disease, are currently a global health problem
Effects of bortezomib on atherosclerosis The results showed that the highest atherosclerosis score was in the atherosclerosis group, while the lowest was in the control group
Most of the groups induced by atherosclerosis and given bortezomib were in the initiation stage marked by the presence of foam cells
Summary
Cardiovascular diseases (CDVs), consisting of coronary heart disease and cerebrovascular disease ( ischemic stroke), are currently a global health problem. Cardiovascular diseases are caused mainly by atherosclerosis, which is an inflammatory process mostly occurring in medium-sized arteries, such as the coronary arteries, carotid arteries, thoracic aorta, and abdominal aorta. Previous studies have shown that the highest proteasome expression in atherosclerotic lesions is at the progression stage. Adhesion molecules play a role in the progression stage of atherosclerosis, but no studies have analyzed the effect of proteasome inhibitors on the expression of adhesion molecules at this stage. Methods: This experimental study aimed to analyze the effect of a proteasome inhibitor, namely bortezomib, on the vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule (ICAM-1) expressions in blood vessels of rat model of atherosclerosis at the progression stage. Conclusions: Administration of bortezomib 50μg/kg for four days in progressive atherosclerosis model rats can inhibit VCAM-1 expression, it does not affect ICAM-1 expression and cannot inhibit atherosclerotic lesion formation
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