Rapid over-activation of β-adrenergic receptors (β-AR) following acute stress initiates cardiac inflammation and injury by activating interleukin-18 (IL-18),however,the process of inflammation cascades has not been ...Rapid over-activation of β-adrenergic receptors (β-AR) following acute stress initiates cardiac inflammation and injury by activating interleukin-18 (IL-18),however,the process of inflammation cascades has not been fully illustrated.The present study aimed to determine the mechanisms of cardiac inflammatory amplification following acute sympathetic activation.With bioinformatics analysis,galectin-3 was identified as a potential key downstream effector of β-AR and IL-18 activation.The serum level of galectin-3 was positively correlated with norepinephrine or IL-18 in patients with chest pain.In the heart of mice treated with β-AR agonist isoproterenol (ISO,5 mg kg^(-1)),galectin-3 expression was upregulated markedly later than IL-18 activation,and Nlrp3^(-/-)and Il18^(-/-)mice did not show ISO-induced galectin-3 upregulation.It was further revealed that cardiomyocyte-derived IL-18 induced galectin-3 expression in macrophages following ISO treatment.Moreover,galectin-3deficiency suppressed ISO-induced cardiac inflammation and fibrosis without blocking ISO-induced IL-18 increase.Treatment with a galectin-3 inhibitor,but not a β-blocker,one day after ISO treatment effectively attenuated cardiac inflammation and injury.In conclusion,galectin-3 is upregulated to exaggerate cardiac inflammation and injury following acute β-AR activation,a galectin-3 inhibitor effectively blocks cardiac injury one day after β-AR insult.展开更多
This study investigated the effect of exercise training on insulin resistance and serum and adipose TNF-αin high-fat diet-induced insulin-resistant rats.Thirty male Wistar rats were randomly divided into two groups:n...This study investigated the effect of exercise training on insulin resistance and serum and adipose TNF-αin high-fat diet-induced insulin-resistant rats.Thirty male Wistar rats were randomly divided into two groups:normal control group(NC;n=8)that accepted normal chow and high-fat diet group(HF;n=22)that fed on high-fat diet to induce insulin resistance model.The HF group was randomly assigned to two subgroups after 18 weeks:sedentary group(SE;n=10)and exercise training group(ET;n=12)that performed swimming exercise training for 6 weeks,while both groups continued high-fat diet.Changes of body weight,lipid profile,and fasting plasma glucose and insulin were measured.The insulin sensitivity index(ISI)was calculated.Serum concentration of TNF-αwas detected by ELISA.The expression of TNF-αmRNA and protein in adipose tissue was examined by using real-timefluorescence quantitative polymerase chain reaction(PCR)and Western blot,respectively.After 18 weeks,compared with the NC group,body weight,blood lipid,glucose,and insulin in the HF group were significantly elevated,while the ISI decreased obviously,which suggested that insulin resistance appeared in the HF group.After exercise training for 6 weeks,compared with the SE group,both ISI and serum TNF-αconcentration in the ET group were decreased significantly;however,the expression levels of TNF-αmRNA and protein in adipose tissue increased by 27.5%and 20.5%,respectively.In conclusion,exercise training ameliorates insulin resis-tance.The reduction of the level of serum TNF-αand the increased expression of TNF-αin adipose tissue by exercise training may be involved in this mechanism.展开更多
基金supported by the National Key R&D Program of China (2021YFF0501401)the National Natural Science Foundation of China (82030072)+5 种基金the Michigan Medicine-PKUHSC Joint Institute for Translational and Clinical Research (BMU2019JI007)the Fundamental Research Funds for the Central Universitiesthe National Natural Science Foundation of China (81830009, 81822003)the Beijing Municipal Natural Science Foundation (7191013)the Key Clinical Projects of Peking University Third Hospital (BYSYZD2019022)CAMS Innovation Fund for Medical Sciences to (2021-I2M-5-003)。
文摘Rapid over-activation of β-adrenergic receptors (β-AR) following acute stress initiates cardiac inflammation and injury by activating interleukin-18 (IL-18),however,the process of inflammation cascades has not been fully illustrated.The present study aimed to determine the mechanisms of cardiac inflammatory amplification following acute sympathetic activation.With bioinformatics analysis,galectin-3 was identified as a potential key downstream effector of β-AR and IL-18 activation.The serum level of galectin-3 was positively correlated with norepinephrine or IL-18 in patients with chest pain.In the heart of mice treated with β-AR agonist isoproterenol (ISO,5 mg kg^(-1)),galectin-3 expression was upregulated markedly later than IL-18 activation,and Nlrp3^(-/-)and Il18^(-/-)mice did not show ISO-induced galectin-3 upregulation.It was further revealed that cardiomyocyte-derived IL-18 induced galectin-3 expression in macrophages following ISO treatment.Moreover,galectin-3deficiency suppressed ISO-induced cardiac inflammation and fibrosis without blocking ISO-induced IL-18 increase.Treatment with a galectin-3 inhibitor,but not a β-blocker,one day after ISO treatment effectively attenuated cardiac inflammation and injury.In conclusion,galectin-3 is upregulated to exaggerate cardiac inflammation and injury following acute β-AR activation,a galectin-3 inhibitor effectively blocks cardiac injury one day after β-AR insult.
基金supported by a grant from Hubei Provincial Science and Technology Foundation(No.2005AA30C133).
文摘This study investigated the effect of exercise training on insulin resistance and serum and adipose TNF-αin high-fat diet-induced insulin-resistant rats.Thirty male Wistar rats were randomly divided into two groups:normal control group(NC;n=8)that accepted normal chow and high-fat diet group(HF;n=22)that fed on high-fat diet to induce insulin resistance model.The HF group was randomly assigned to two subgroups after 18 weeks:sedentary group(SE;n=10)and exercise training group(ET;n=12)that performed swimming exercise training for 6 weeks,while both groups continued high-fat diet.Changes of body weight,lipid profile,and fasting plasma glucose and insulin were measured.The insulin sensitivity index(ISI)was calculated.Serum concentration of TNF-αwas detected by ELISA.The expression of TNF-αmRNA and protein in adipose tissue was examined by using real-timefluorescence quantitative polymerase chain reaction(PCR)and Western blot,respectively.After 18 weeks,compared with the NC group,body weight,blood lipid,glucose,and insulin in the HF group were significantly elevated,while the ISI decreased obviously,which suggested that insulin resistance appeared in the HF group.After exercise training for 6 weeks,compared with the SE group,both ISI and serum TNF-αconcentration in the ET group were decreased significantly;however,the expression levels of TNF-αmRNA and protein in adipose tissue increased by 27.5%and 20.5%,respectively.In conclusion,exercise training ameliorates insulin resis-tance.The reduction of the level of serum TNF-αand the increased expression of TNF-αin adipose tissue by exercise training may be involved in this mechanism.
