Sympathetic nerve and vagus nerve remodeling play an important part in cardiac function post-myocardial infarction （MI）. Increasing evidence indicates that neuregulin-1 （NRG-1） improves cardiac function following ...Sympathetic nerve and vagus nerve remodeling play an important part in cardiac function post-myocardial infarction （MI）. Increasing evidence indicates that neuregulin-1 （NRG-1） improves cardiac function following heart failure. Since its impact on cardiac function and neural remodeling post-MI is poorly understood, we aimed to investigate the role of NRG-1 in autonomic nervous system remodeling post-MI. Forty-five Sprague-Dawley rats were equally randomized into three groups： sham （with the left anterior descending coronary artery exposed but without ligation）, MI （left anterior descending coronary artery ligation）, and MI plus NRG-1 （left anterior descending coronary artery ligation followed by intraperitoneal injection of NRG-1 （10 lag/kg, once daily for 7 days））. At 4 weeks after MI, echocardi- ography was used to detect the rat cardiac function by measuring the left ventricular end-systolic inner diameter, left ventricular diastolic diameter, left ventricular end-systolic volume, left ventricular end-diastolic volume, left ventricular ejection fraction, and left ventricular fractional shortening, mRNA and protein expression levels of tyrosine hydroxylase, growth associated protein-43 （neuronal specific pro- tein）, nerve growth factor, choline acetyltransferase （vagus nerve marker）, and vesicular acetylcholine transporter （cardiac vagal nerve fiber marker） in ischemic myocardia were detected by real-time PCR and western blot assay to assess autonomous nervous remodeling. After MI, the rat cardiac function deteriorated significantly, and it was significantly improved after NRG-1 injection. Compared with the MI group, mRNA and protein levels of tyrosine hydroxylase and growth associated protein-43, as well as choline acetyltransferase mRNA level significantly decreased in the MI plus NRG-1 group, while mRNA and protein levels of nerve growth factor and vesicular acetylcholine transporters, as well as choline acetyltransferase protein level slightly decreased. Our results indicate that NRG- 1 can improve cardiac function and regulate sympathetic and vagus nerve remodeling post-MI, thus reaching a new balance of the autonomic nervous system to protect the heart from injury.展开更多
This study aimed to investigate whether fetal growth trajectories(FGTs)could predict early childhood development,indicate intrauterine metabolic changes,and explore potential optimal and suboptimal FGTs.FGTs were deve...This study aimed to investigate whether fetal growth trajectories(FGTs)could predict early childhood development,indicate intrauterine metabolic changes,and explore potential optimal and suboptimal FGTs.FGTs were developed by using an unsupervised machine-learning approach.Children’s neurodevelopment,anthropometry,and respiratory outcomes in thefirst 6 years of life were assessed at different ages.In a subgroup of participants,we conducted a metabolomics analysis of cord blood to reveal the metabolic features of FGTs.We identified 6 FGTs:early decelerating,early decelerating with late catch-up growth,early accelerating,early accelerating with late medium growth,late decelerating,and late accelerating.The early accelerating with late medium growth pattern might be the optimal FGT due to its associations with better psychomotor development,mental development,intelligence quotient,and lung function and a lower risk of behaviour and respiratory problems.Compared with the optimal FGT,early decelerating and late decelerating FGTs were associated with poor neurodevelopment and lung function,while early accelerating FGT was associated with more severe autistic symptoms,poor lung function,and increased risks of overweight/obesity.Metabolic alterations were enriched in amino acid metabolism for early decelerating and late decelerating FGTs,whereas altered metabolites were enriched in lipid metabolism for early accelerating FGT.Thesefindings suggest that FGTs are predictors of early life development and may indicate intrauterine adaptive metabolism.The discovery of optimal and suboptimal FGTs provides potential clues for the early identification and intervention of fetal origin dysplasia or disease,but further research on related mechanisms is still needed.展开更多
基金supported by a grant from the National Key Basic Research Development Program,the“973”Program,No.2012CB518604the National Natural Science Foundation of China,No.81260052+1 种基金the Natural Science Foundation of Hubei Province,No.2014CKB497,2014BKB075,and 2015BKA339the Natural Science Foundation of Henan Province of China,No.201602262
文摘Sympathetic nerve and vagus nerve remodeling play an important part in cardiac function post-myocardial infarction （MI）. Increasing evidence indicates that neuregulin-1 （NRG-1） improves cardiac function following heart failure. Since its impact on cardiac function and neural remodeling post-MI is poorly understood, we aimed to investigate the role of NRG-1 in autonomic nervous system remodeling post-MI. Forty-five Sprague-Dawley rats were equally randomized into three groups： sham （with the left anterior descending coronary artery exposed but without ligation）, MI （left anterior descending coronary artery ligation）, and MI plus NRG-1 （left anterior descending coronary artery ligation followed by intraperitoneal injection of NRG-1 （10 lag/kg, once daily for 7 days））. At 4 weeks after MI, echocardi- ography was used to detect the rat cardiac function by measuring the left ventricular end-systolic inner diameter, left ventricular diastolic diameter, left ventricular end-systolic volume, left ventricular end-diastolic volume, left ventricular ejection fraction, and left ventricular fractional shortening, mRNA and protein expression levels of tyrosine hydroxylase, growth associated protein-43 （neuronal specific pro- tein）, nerve growth factor, choline acetyltransferase （vagus nerve marker）, and vesicular acetylcholine transporter （cardiac vagal nerve fiber marker） in ischemic myocardia were detected by real-time PCR and western blot assay to assess autonomous nervous remodeling. After MI, the rat cardiac function deteriorated significantly, and it was significantly improved after NRG-1 injection. Compared with the MI group, mRNA and protein levels of tyrosine hydroxylase and growth associated protein-43, as well as choline acetyltransferase mRNA level significantly decreased in the MI plus NRG-1 group, while mRNA and protein levels of nerve growth factor and vesicular acetylcholine transporters, as well as choline acetyltransferase protein level slightly decreased. Our results indicate that NRG- 1 can improve cardiac function and regulate sympathetic and vagus nerve remodeling post-MI, thus reaching a new balance of the autonomic nervous system to protect the heart from injury.
基金supported by the National Natural Science Foundation of China(U21A20397,22236001,42277428)the Program for HUST Academic Frontier Youth Team(2018QYTD12).
文摘This study aimed to investigate whether fetal growth trajectories(FGTs)could predict early childhood development,indicate intrauterine metabolic changes,and explore potential optimal and suboptimal FGTs.FGTs were developed by using an unsupervised machine-learning approach.Children’s neurodevelopment,anthropometry,and respiratory outcomes in thefirst 6 years of life were assessed at different ages.In a subgroup of participants,we conducted a metabolomics analysis of cord blood to reveal the metabolic features of FGTs.We identified 6 FGTs:early decelerating,early decelerating with late catch-up growth,early accelerating,early accelerating with late medium growth,late decelerating,and late accelerating.The early accelerating with late medium growth pattern might be the optimal FGT due to its associations with better psychomotor development,mental development,intelligence quotient,and lung function and a lower risk of behaviour and respiratory problems.Compared with the optimal FGT,early decelerating and late decelerating FGTs were associated with poor neurodevelopment and lung function,while early accelerating FGT was associated with more severe autistic symptoms,poor lung function,and increased risks of overweight/obesity.Metabolic alterations were enriched in amino acid metabolism for early decelerating and late decelerating FGTs,whereas altered metabolites were enriched in lipid metabolism for early accelerating FGT.Thesefindings suggest that FGTs are predictors of early life development and may indicate intrauterine adaptive metabolism.The discovery of optimal and suboptimal FGTs provides potential clues for the early identification and intervention of fetal origin dysplasia or disease,but further research on related mechanisms is still needed.
