Probucol Protects Against Atherosclerosis Through Induction Of Hemeoxygenase-1

Objective(1)To set up an animal model of abdominal atherosclerotic plaques;(2) To determine the effect of probucol on AS progression and plaque stabilization;(3) To observe the effect of probucol on plaque pathologic condition and plasm levels of inflammational and oxidation factors;(4) To explore the possible mechanism underlying probucol’s beneficial properties, so as to provide theoretical bases for preventing ACS.Research objects and methodsAtherosclerotic plaques were induced in aortas of60male New Zealand White rabbits by atherogenic diet for12weeks after endothelial injury. Rabbits were then randomized into4groups which received, respectively, no treatment, probucol, Sn protoporphyrin Ⅸ (SnPP Ⅸ), or probucol plus SnPP Ⅸ for12weeks. Serological, pathological, immunohistochemical and gene expression studies were performed.The resultsProbucol significantly induced HO-1mRNA, protein, and enzyme activity in atherosclerotic plaques. This induction was correlated with a reduction in the progression of plaque size. Furthermore, this induction resulted in features of plaque stability such as increased fibrous cap thickness and less macrophage infiltration. Moreover, the serum levels of oxidized low density lipoprotein and proinflammatory factors, including matrix metalloproteinase-9, interleukin-18and high sensitive C-reactive protein were remarkably reduced by probucol. In contrast, inhibition of HO-1by SnPP IX augmented plaque progression and vulnerability and significantly reduced the effects of probucol.ConclusionOur results demonstrate that probucol treatment may inhibit atherosclerosis progression and promote plaque stability by induction of HO-1.