Abnormal TPM2 expression is involved in regulation of atherosclerosis progression via mediating RhoA signaling .

INTRODUCTION

Ox-LDL (oxidized low-density lipoprotein)-induced endothelial cell injury and dysfunction of vascular smooth muscle cells play critical roles in the development of atherosclerosis (AS). Tropomyosin 2 (TPM2) has been implicated in cardiac diseases, but its critical role and regulatory mechanism in AS progression have not yet been elucidated.

MATERIAL AND METHODS

The expression of TPM2 was investigated in AS tissues. Ox-LDL was used to construct an AS model based on endothelial and vascular smooth muscle cells (HAECs and VSMCs). An overexpression assay was performed to evaluate the role of TPM2 in AS. Meanwhile, the involvement of the RhoA pathway in TPM2-mediated AS progression was evaluated using narciclasine.

RESULTS

Tropomyosin 2 was dramatically upregulated in both AS tissues and ox-LDL-induced HAECs. Overexpression of TPM2 attenuated ox-LDL-stimulated cell growth depression, inflammatory and adhesive responses in HAECs, as well as oxidative stress and mitochondrial dysfunction. Additionally, VSMCs, impacted by TPM2-overexpressed HAECs, showed alleviated cellular processes which were abnormally activated by ox-LDL. Furthermore, depressed activation of the RhoA pathway was found in TPM2-overexpressed HAECs and activating the signaling rescued these effects of TPM2 exerted on ox-LDL-stimulated HAECs and VSMCs.

CONCLUSIONS

TPM2 had an advantageous impact on ox-LDL-induced AS progression by mediating the RhoA pathway. This evidence might contribute to the therapy of AS.