Background:Ketone body metabolism can improve cardiomyocytes metabolism and reduce myocardial oxygen consumption;however,its role in the short-term prognosis of patients with acute myocardial infarction combined with ...Background:Ketone body metabolism can improve cardiomyocytes metabolism and reduce myocardial oxygen consumption;however,its role in the short-term prognosis of patients with acute myocardial infarction combined with heart failure has not been clearly elucidated.The aim of this study was to investigate the effect ofβ-hydroxybutyric acid,the main component of ketone bodies,on the shortterm prognosis of patients with acute myocardial infarction combined with heart failure.Methods:This was a retrospective observational study that enrolled patients admitted to the Qilu Hospital of Shandong University for acute myocardial infarction combined with heart failure between January 1,2019,and December 31,2022.According to whetherβ-hydroxybutyric acid was elevated or not,subjects were divided into aβ-hydroxybutyric acid elevated and nonelevated groups,to observe the difference in cardiac function improvement between the two groups.Results:This study included a total of 260 patients,of which 170 exhibited elevated levels ofβ-hydroxybutyric acid.Compared to the patients in the nonelevated group,patients in the elevatedβ-hydroxybutyric acid group had higher plasma levels of creatine kinase myocardial band and greater Gensini scores.Multivariate logistic regression analysis indicated that an increase inβ-hydroxybutyric acid levels(odds ratio:3.076;95%confidence intervals:1.479–6.395;P=0.003)is an independent protective factor affecting the prognosis of cardiac function in patients with acute myocardial infarction combined with heart failure.Conclusion:In patients with acute myocardial infarction combined with heart failure,plasmaβ-hydroxybutyric acid serves as an independent protective factor for short-term improvement in cardiac function.展开更多
Background:Visceral adipose tissue-derived serine protease inhibitor(vaspin),a secretory adipokine,protects against insulin resistance.Recent studies have demonstrated that serum vaspin levels are decreased in patient...Background:Visceral adipose tissue-derived serine protease inhibitor(vaspin),a secretory adipokine,protects against insulin resistance.Recent studies have demonstrated that serum vaspin levels are decreased in patients with coronary artery disease and that vaspin protects against myocardial ischemia-reperfusion injury and atherosclerosis.However,it remains unclear whether vaspin exerts specific effects on pathological cardiac hypertrophy.Methods:An in vivo study was conducted using a cardiac hypertrophy model established by subcutaneous injection of isoproterenol(ISO)in C57BL/6 and vaspin-ko mice.Rapamycin was administered intraperitoneally to mice,for further study.H9c2 cells and neonatal rat ventricular myocytes(NRVMs)were treated with ISO to induce hypertrophy.Human vaspin fusion protein,the proteasome inhibitor MG132,and chloroquine diphosphate were used for further mechanistic studies.Results:Here,we provide the first evidence that vaspin knockdown results in markedly exaggerated cardiac hypertrophy,fibrosis,and cardiomyocyte senescence in mice treated with ISO.Conversely,the administration of exogenous recombinant human vaspin protected NRVMs in vitro against ISO-induced hypertrophy and senescence.Furthermore,vaspin significantly potentiated the ISO-induced decrease in autophagy.Both rapamycin and chloroquine diphosphate regulated autophagy in vivo and in vitro,respectively,and participated in vaspin-mediated cardioprotection.Moreover,the PI3K-AKT-mTOR pathway plays a critical role in vaspin-mediated autophagy in cardiac tissues and NRVMs.Our data showed that vaspin downregulated the p85 and p110 subunits of PI3K by linking p85 and p110 to NEDD4L-mediated ubiquitination degradation.Conclusion:Our results show,for the first time,that vaspin functions as a critical regulator that alleviates pathological cardiac hypertrophy by regulating autophagy-dependent myocardial senescence,providing potential preventive and therapeutic targets for pathological cardiac hypertrophy.展开更多
基金supported by the State Key Program of the National Natural Science Foundation of China(82030059)National Natural Science Foundation of China(82172178,82072144,81873950,81873953,81300219,81671951)+6 种基金National Key R&D Program of China(2020YFC1512700,2020YFC1512705,2020YFC1512703)National S&T Fundamental Resources Investigation Project(2018FY100600,2018FY100602)Natural Science Foundation of Shandong Province(ZR2022MH078)Key R&D Program of Shandong Province(2019GSF108131)Taishan Pandeng Scholar Program of Shandong Province(tspd20181220)Taishan Young Scholar Program of Shandong Province(tsqn202103173,tsqn20161065,tsqn201812129)Youth Top-Talent Project of National Ten Thousand Talents Plan,and Qilu Young Scholar Program.
文摘Background:Ketone body metabolism can improve cardiomyocytes metabolism and reduce myocardial oxygen consumption;however,its role in the short-term prognosis of patients with acute myocardial infarction combined with heart failure has not been clearly elucidated.The aim of this study was to investigate the effect ofβ-hydroxybutyric acid,the main component of ketone bodies,on the shortterm prognosis of patients with acute myocardial infarction combined with heart failure.Methods:This was a retrospective observational study that enrolled patients admitted to the Qilu Hospital of Shandong University for acute myocardial infarction combined with heart failure between January 1,2019,and December 31,2022.According to whetherβ-hydroxybutyric acid was elevated or not,subjects were divided into aβ-hydroxybutyric acid elevated and nonelevated groups,to observe the difference in cardiac function improvement between the two groups.Results:This study included a total of 260 patients,of which 170 exhibited elevated levels ofβ-hydroxybutyric acid.Compared to the patients in the nonelevated group,patients in the elevatedβ-hydroxybutyric acid group had higher plasma levels of creatine kinase myocardial band and greater Gensini scores.Multivariate logistic regression analysis indicated that an increase inβ-hydroxybutyric acid levels(odds ratio:3.076;95%confidence intervals:1.479–6.395;P=0.003)is an independent protective factor affecting the prognosis of cardiac function in patients with acute myocardial infarction combined with heart failure.Conclusion:In patients with acute myocardial infarction combined with heart failure,plasmaβ-hydroxybutyric acid serves as an independent protective factor for short-term improvement in cardiac function.
基金the State Key Program of the National Natural Science Foundation of China(82030059)National Natural Science Foundation of China(82172178,82072144,81873950,81873953,81300219,81671951)+6 种基金National Key R&D Program of China(2020YFC1512700,2020YFC1512705,2020YFC1512703)National S&T Fundamental Resources Investigation Project(2018FY100600,2018FY100602)Natural Science Foundation of Shandong Province(ZR2022MH078)Key R&D Program of Shandong Province(2019GSF108131)Taishan Pandeng Scholar Program of Shandong Province(tspd20181220)Taishan Young Scholar Program of Shandong Province(tsqn202103173,tsqn20161065,tsqn201812129)Youth Top-Talent Project of National Ten Thousand Talents Plan,and Qilu Young Scholar Program.
文摘Background:Visceral adipose tissue-derived serine protease inhibitor(vaspin),a secretory adipokine,protects against insulin resistance.Recent studies have demonstrated that serum vaspin levels are decreased in patients with coronary artery disease and that vaspin protects against myocardial ischemia-reperfusion injury and atherosclerosis.However,it remains unclear whether vaspin exerts specific effects on pathological cardiac hypertrophy.Methods:An in vivo study was conducted using a cardiac hypertrophy model established by subcutaneous injection of isoproterenol(ISO)in C57BL/6 and vaspin-ko mice.Rapamycin was administered intraperitoneally to mice,for further study.H9c2 cells and neonatal rat ventricular myocytes(NRVMs)were treated with ISO to induce hypertrophy.Human vaspin fusion protein,the proteasome inhibitor MG132,and chloroquine diphosphate were used for further mechanistic studies.Results:Here,we provide the first evidence that vaspin knockdown results in markedly exaggerated cardiac hypertrophy,fibrosis,and cardiomyocyte senescence in mice treated with ISO.Conversely,the administration of exogenous recombinant human vaspin protected NRVMs in vitro against ISO-induced hypertrophy and senescence.Furthermore,vaspin significantly potentiated the ISO-induced decrease in autophagy.Both rapamycin and chloroquine diphosphate regulated autophagy in vivo and in vitro,respectively,and participated in vaspin-mediated cardioprotection.Moreover,the PI3K-AKT-mTOR pathway plays a critical role in vaspin-mediated autophagy in cardiac tissues and NRVMs.Our data showed that vaspin downregulated the p85 and p110 subunits of PI3K by linking p85 and p110 to NEDD4L-mediated ubiquitination degradation.Conclusion:Our results show,for the first time,that vaspin functions as a critical regulator that alleviates pathological cardiac hypertrophy by regulating autophagy-dependent myocardial senescence,providing potential preventive and therapeutic targets for pathological cardiac hypertrophy.
