Tongxinluo may stabilize atherosclerotic plaque via multiple mechanisms scanning by genechip

Abstract

Background: Chinese traditional medicine Tongxinluo capsule (TXL) has been widely used for cardiovascular diseases. Both clinical and basic studies showed that TXL had effective effects on atherosclerosis. However, the mechanism researches were relatively scattered. This study was aimed to fully evaluate the potential mechanisms of TXL on atherosclerosis as a whole.

Method: One hundred apoE-/- mice (male, 12 weeks old) were randomly divided into five groups (n = 20 each group) Mice in the control group were fed normal diet and mice in the other four groups (intervention groups) were fed high fat diet. The intervention groups were randomly divided into normal saline (NS) group and TXL treatment groups, and the latter were further divided into three subgroups: low-dose TXL (TXL-L), medium-dose TXL (TXL-M) and high-dose TXL (TXL-H), with TXL dosage at 0.38, 0.75, 1.5 g/kg/d by gavage, respectively. After sixteen weeks of intervention, all mice underwent euthanasia. Gene expression profiles with aortic tissues were determined by genechip. A Gene Ontology (GO) analysis was performed to interpret the functional implications of altered genes.

Result: Histological and morphological analysis demonstrated that TXL at different doses all reduced plaque burden and plaque size. The expressions of IL-6, TNF-ɑ and MMP-2 were significantly decreased in the TXL intervention groups compared with control. In atherosclerotic lesions of TXL groups 3284 genes altered compared with control, and 632 genes changed in the TXL-H group compared with the NS group. Of these genes, 48 showed a decrease which were high in atherosclerosis, and 56 showed a increase which were low in atherosclerosis after TXL intervention. Significantly altered genes were found to be involved in the aspects of hormone secretion, protein binding, lipid metabolic, fatty acid metabolic immune system process, and inflammatory response.

Conclusion: TXL has effects on inhibiting atherosclerosis development and stablizing plaque. The comprehensive mechanisms, in addition to inflammation and lipid metabolism, might also involve cell physical function, hormone secretion, protein binding, and immune response process.

Keywords: Atherosclerosis; Genechip; Inflammation; Tongxinluo; Vulnerable plaque.