Tao Zeng1, Jun Yuan1, Jianting Gan1, Yu Liu1, Lei Shi1, Zhengde Lu1, Yan Xue1, Rixin Xiong1, Min Huang2, Zicong Yang1, Yingzhong Lin3, Ling Liu4. 1. Department of Cardiology, The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, China. 2. Department of Cardiology, The Second Affiliated Hospital of Guilin Medical University, Guilin, China. 3. Department of Cardiology, The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, China. Electronic address: yingzhonglin@126.com. 4. Department of Cardiology, The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, China. Electronic address: gxliu@126.com.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
BACKGROUND: 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. METHODS:TSP-1 levels were detected in aortas collected from control subjects and ADpatients. The TSP-1, interleukin (IL) 6, matrix metalloproteinase (MMP) 2, and MMP9 levels in plasma from non-ADpatients and ADpatients were measured. In addition, the effects of recombinant mouseTSP-1 protein on macrophage differentiation and smooth muscle cell (SMC) apoptosis were investigated. RESULTS: Compared with the aortas from control subjects, aortas from ADpatients 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 ADpatients than in non-ADpatients, and plasma IL-6, MMP2, and MMP9 levels were positively correlated with TSP-1 levels in ADpatients. 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 mouseTSP-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. CONCLUSIONS:TSP-1 level is significantly increased in ADpatients and might participate in AD via promoting classically activated macrophage (M1) macrophage differentiation and SMC apoptosis.
Authors: Louis Saddic; Amanda Orosco; Dongchuan Guo; Dianna M Milewicz; Dana Troxlair; Richard Vander Heide; David Herrington; Yue Wang; Ali Azizzadeh; Sarah J Parker Journal: JVS Vasc Sci Date: 2022-01-22