Expression of MMP2, MMP9, TIMP2 and TIMP3 genes in aortic dissection.

ABSTRACT

Thoracic aortic dissection (TAD) is a highly lethal disease occurring inside the aortic wall and is characterized by matrix degradation. Matrix metalloproteinases (MMPs) are members of a large endopeptidase family that function in the degradation of the extracellular matrix (ECM) proteins, the maintenance of the ECM, and the regulation of signaling in the aorta. MMPs are found in tissue with their natural inhibitors. Tissue inhibitors of metalloproteinases (TIMPs) are actively involved in both the activation and inhibition of MMPs. The present study was designed to determine the mRNA level gene expression differences of MMP2, MMP9, TIMP2 and TIMP3, which are considered to have an essential role in TAD, in aortic tissue and circulating monocyte cells. For the purpose of the present study, aortic vascular tissue and peripheral blood-derived monocyte cells were obtained from 10 patients with TAD and 10 control individuals. The gene expression levels of targeted genes (MMP2, MMP9, TIMP2 and TIMP3) were examined by droplet digital PCR. In research results, decreased expression of MMP9, TIMP2 and TIMP3 genes (P=0.043, P=0.009 and P=0.028, respectively) and increased ratio of MMP2/TIMP3 (P=0.012) were obtained in the aortic tissue. No changes were observed in terms of gene expression in monocyte cells. When the results obtained were evaluated within the framework of TAD pathogenesis, it was concluded that expression changes in MMP9, TIMP2 and TIMP3 genes may provide a sensitive environment in aortic tissue and may be associated with TAD formation. In addition, since the expression ratios of MMPs and TIMPs may reflect disease development, it was considered that the evaluation of MMPs along with TIMPs may be an appropriate and informative approach for future studies.