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

Previous 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. TSP-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. Compared 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. TSP-1 level is significantly increased in AD patients and might participate in AD via promoting classically activated macrophage (M1) macrophage differentiation and SMC apoptosis. Des études antérieures ont montré que la thrombospondine-1 (TSP-1) joue un rôle dans les maladies cardiovasculaires comme l’athérosclérose et l’anévrisme de l’aorte abdominale. Toutefois, les taux d’expression de la TSP-1 chez les patients présentant une dissection aortique (DA) demeurent inconnus. Les concentrations de TSP-1 ont été mesurées dans des aortes prélevées chez des sujets témoins et des patients présentant une DA. Les concentrations plasmatiques de TSP-1, d’interleukine-6 (IL-6) et de métalloprotéase matricielle-2 et -9 (MMP-2 et MMP-9) ont été mesurées chez des patients atteints de DA et chez des patients non atteints. De plus, nous avons étudié les effets de la protéine TSP-1 murine recombinante (rmTSP-1) sur la différenciation des macrophages et sur l’apoptose des cellules des muscles lisses (CML). Comparativeme