Fang Wang1, Chang Li1, Feng Hua Ding1, Ying Shen1, Jie Gao1, Zhu Hui Liu2, Jia Wei Chen2, Rui Yan Zhang1, Wei Feng Shen3, Xiao Qun Wang4, Lin Lu5. 1. Department of Cardiology, Rui Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, PR China. 2. Institute of Cardiovascular Diseases, Shanghai Jiao-Tong University School of Medicine, Shanghai, PR China. 3. Department of Cardiology, Rui Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, PR China; Institute of Cardiovascular Diseases, Shanghai Jiao-Tong University School of Medicine, Shanghai, PR China. 4. Department of Cardiology, Rui Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, PR China; Institute of Cardiovascular Diseases, Shanghai Jiao-Tong University School of Medicine, Shanghai, PR China. Electronic address: Xiaoqun_Wang@hotmail.com. 5. Department of Cardiology, Rui Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, PR China; Institute of Cardiovascular Diseases, Shanghai Jiao-Tong University School of Medicine, Shanghai, PR China. Electronic address: rjlulin1965@163.com.
Abstract
BACKGROUND AND AIMS: In-stent restenosis (ISR) remains a major limitation of percutaneous coronary intervention despite improvements in stent design and pharmacological agents, whereas the mechanism of ISR has not been fully clarified. In the present study, we sought to investigate the potential association of serum soluble TREM-1 (sTREM-1) levels with the incidence of ISR. The role of TREM-1 was evaluated in cultured vascular smooth muscle cells (VSMCs). METHODS: Out of 1683 patients undergoing coronary intervention and follow-up coronary angiography after approximately one year, 130 patients were diagnosed with ISR, and 150 gender- and age-matched patients with no ISR were randomly included as controls. Levels of sTREM-1 were determined by ELISA. The role of TREM-1 signaling in the activation of VSMCs was tested. RESULTS: Serum sTREM-1 concentrations were significantly elevated in patients with than without ISR. Multivariable logistic regression analysis showed that sTREM-1, besides conventional factors, was independently associated with the incidence of ISR. Evident expression of TREM-1 in VSMCs was detected in the neointimal and medial layers of stenotic lesions of mouse carotid ligation models. In cultured VSMCs, expression of TREM-1 was significantly induced upon exposure to lipopolysaccharide. Blocking of TREM-1 with a synthetic inhibitory peptide LP17 dramatically inhibited, whereas TREM-1-activating antibody promoted cellular inflammation, proliferation and migration in VSMCs. CONCLUSIONS: These data suggest that TREM-1 is a predictive biomarker of ISR and an important mediator of cellular inflammation, migration, and proliferation in VSMCs. Pharmacological inhibition of TREM-1 may serve as a promising approach to attenuate the progression of ISR.
BACKGROUND AND AIMS: In-stent restenosis (ISR) remains a major limitation of percutaneous coronary intervention despite improvements in stent design and pharmacological agents, whereas the mechanism of ISR has not been fully clarified. In the present study, we sought to investigate the potential association of serum soluble TREM-1 (sTREM-1) levels with the incidence of ISR. The role of TREM-1 was evaluated in cultured vascular smooth muscle cells (VSMCs). METHODS: Out of 1683 patients undergoing coronary intervention and follow-up coronary angiography after approximately one year, 130 patients were diagnosed with ISR, and 150 gender- and age-matched patients with no ISR were randomly included as controls. Levels of sTREM-1 were determined by ELISA. The role of TREM-1 signaling in the activation of VSMCs was tested. RESULTS: Serum sTREM-1 concentrations were significantly elevated in patients with than without ISR. Multivariable logistic regression analysis showed that sTREM-1, besides conventional factors, was independently associated with the incidence of ISR. Evident expression of TREM-1 in VSMCs was detected in the neointimal and medial layers of stenotic lesions of mouse carotid ligation models. In cultured VSMCs, expression of TREM-1 was significantly induced upon exposure to lipopolysaccharide. Blocking of TREM-1 with a synthetic inhibitory peptide LP17 dramatically inhibited, whereas TREM-1-activating antibody promoted cellular inflammation, proliferation and migration in VSMCs. CONCLUSIONS: These data suggest that TREM-1 is a predictive biomarker of ISR and an important mediator of cellular inflammation, migration, and proliferation in VSMCs. Pharmacological inhibition of TREM-1 may serve as a promising approach to attenuate the progression of ISR.