Sha-Sha Xing1, Jian Li2, Lin Chen3, Ya-Fei Yang3, Ping-Lin He3, Jun Li4, Jin Yang5. 1. Clinical Drug Trial Center, Affiliated Hospital of Chengdu University, Chengdu University, Chengdu, Sichuan, 610081, PR China. 2. Department of Basic Medicine, Chengdu University School of Medicine, Chengdu, Sichuan, 610106, PR China. 3. Department of Urology, Affiliated Hospital of Chengdu University, Chengdu, Sichuan, 610081, PR China. 4. Clinical Drug Trial Center, Affiliated Hospital of Chengdu University, Chengdu University, Chengdu, Sichuan, 610081, PR China; Department of General Surgery, Affiliated Hospital of Chengdu University, Chengdu University, Chengdu, Sichuan, 610081, PR China. Electronic address: junl_paper@sina.com. 5. Clinical Drug Trial Center, Affiliated Hospital of Chengdu University, Chengdu University, Chengdu, Sichuan, 610081, PR China; Department of Urology, Affiliated Hospital of Chengdu University, Chengdu, Sichuan, 610081, PR China. Electronic address: dr.jinyang@163.com.
Abstract
OBJECTIVE: Endothelial cellular senescence is an important contributor to the endothelial dysfunction and atherosclerosis. Our previous studies suggested that salidroside (SAL) can alleviate atherosclerosis and protect endothelial cells against oxidative stress induced damage. However, the effect and mechanism of SAL on endothelial cellular senescence is still unclear. Here, we investigated the underlying mechanisms of SAL on preventing endothelial cellular premature senescence. METHODS AND RESULTS: We established a hyperhomocysteinemia (HHcy)mouse model via high methionine diet (HMD) to explore the protective effect of SAL. According to our results, the HMD elevated the concentration of serum homocysteine. HHcy induced the collagen deposition and the up-regulation of senescence markers, i.e. p16INK4A and p21CIP1, in intima-medial of aorta. In addition, SAL also inhibited the expression of CD68 and intercellular adhesion molecule 1 (ICAM1) in aorta. In senescent human umbilical vein endothelial cells (HUVECs) induced by H2O2, SAL treatment alleviated the expression of p16INK4A and p21CIP1 and reduced the activity of senescence-associated (SA)-β-gal. CONCLUSION: our data suggested that SAL decreased the expression of inflammatory cytokines and up-regulated the expression of SIRT3, which might be the underlying mechanism of SAL on preventing endothelial cells from premature senescence.
OBJECTIVE: Endothelial cellular senescence is an important contributor to the endothelial dysfunction and atherosclerosis. Our previous studies suggested that salidroside (SAL) can alleviate atherosclerosis and protect endothelial cells against oxidative stress induced damage. However, the effect and mechanism of SAL on endothelial cellular senescence is still unclear. Here, we investigated the underlying mechanisms of SAL on preventing endothelial cellular premature senescence. METHODS AND RESULTS: We established a hyperhomocysteinemia (HHcy)mouse model via high methionine diet (HMD) to explore the protective effect of SAL. According to our results, the HMD elevated the concentration of serum homocysteine. HHcy induced the collagen deposition and the up-regulation of senescence markers, i.e. p16INK4A and p21CIP1, in intima-medial of aorta. In addition, SAL also inhibited the expression of CD68 and intercellular adhesion molecule 1 (ICAM1) in aorta. In senescent human umbilical vein endothelial cells (HUVECs) induced by H2O2, SAL treatment alleviated the expression of p16INK4A and p21CIP1 and reduced the activity of senescence-associated (SA)-β-gal. CONCLUSION: our data suggested that SAL decreased the expression of inflammatory cytokines and up-regulated the expression of SIRT3, which might be the underlying mechanism of SAL on preventing endothelial cells from premature senescence.