Thrombospondin 1 Is Increased in the Aorta and Plasma of Patients With Acute Aortic Dissection

Abstract

BackgroundPrevious studies have shown that thrombospondin 1 (TSP-1) is involved in cardiovascular diseases, such as atherosclerosis and abdominal aortic aneurysm. However, TSP-1 expression levels in human aortic dissection (AD) remain unknown. MethodsTSP-1 levels were detected in aortas collected from control subjects and AD patients. The TSP-1, interleukin (IL) 6, matrix metalloproteinase (MMP) 2, and MMP9 levels in plasma from non-AD patients and AD patients were measured. In addition, the effects of recombinant mouse TSP-1 protein on macrophage differentiation and smooth muscle cell (SMC) apoptosis were investigated. ResultsCompared with the aortas from control subjects, aortas from AD patients showed a significant increase in TSP-1 expression, especially in the torn sections. SMCs and endothelial cells produced TSP-1, but SMCs were the main source. TSP-1, IL-6, MMP2, and MMP9 levels were higher in AD patients than in non-AD patients, and plasma IL-6, MMP2, and MMP9 levels were positively correlated with TSP-1 levels in AD patients. Simple linear regression analysis and multivariate linear regression analysis showed that TSP-1 levels were independently correlated with the onset of AD. In cultured cells, recombinant mouse TSP-1 further increased inducible nitric oxide synthase (iNOS) mRNA expression in angiotensin (Ang) II-treated macrophages, whereas it reduced B-cell lymphoma-2 (Bcl2) mRNA levels and increased Bcl2-associated X protein (Bax) mRNA levels in Ang II-treated SMCs. ConclusionsTSP-1 level is significantly increased in AD patients and might participate in AD via promoting classically activated macrophage (M1) macrophage differentiation and SMC apoptosis.