Transcriptional expression profiles of the main proteinases and their regulators in coronary artery ectasia patients' mononuclear cells

Abstract

Objective: Proteolytic enzymes might contribute to coronary artery ectasia (CAE) through the destruction of extracellular matrix (ECM) vessel components. This study aimed to find out if peripheral blood mononuclear cells (PBMCs) served as a source of those proteinases and their regulators.

Method: In this study, transcriptional expression profiles of the main proteinases and their regulators were detected in the PBMCs of CAE patients as follows: (1) matrix metalloproteinases (MMP) 1, 2, 3, 8, 9, 10, 12 and 13; (2) the serine proteinases elastase: cathepsin G and proteinases 3; (3) the cysteine proteinases: cathepsin L and cathepsin S; (4) the main endogenous inhibitors for the above proteinases: tissue inhibitors of metalloproteinase (TIMP) 1 and 2, α1-antitrypsin (α1-PI) and α2-macroglobulin (A2M); (5) twelve cytokines that could regulate the above proteinases.

Result: The characteristic changes in CAE were: (1) MMP1 and MMP9 increased while the serine and cysteine families did not change; (2) the four proteinase inhibitors did not change in the CAE group; (3) among the 12 cytokines, interleukin-1 alpha (IL1A), platelet-derived growth factor (PDGF), interferon gamma (IFNγ) and growth differentiation factor 15 (GDF15) were elevated. Partial correlation analysis showed that MMP1 significantly correlated with IL1A and with IFNγ, and MMP9 correlated with IFNγ and with GDF 15.

Conclusion: PBMCs might participate in the pathological process of CAE by the increased expression of MMP1, MMP9, IL1A, IFNγ and GDF15.

Keywords: Coronary artery ectasia (CAE); elastin fibres; extracellular matrix (ECM); inflammation cytokine; matrix metalloproteinases (MMP); peripheral blood mononuclear cells (PBMCs).