| In the past 20 years,due to the widespread use of percutaneous coronary intervention,the mortality rate of patients with acute myocardial infarction has been significantly reduced,and the mortality rate of in-hospital has been reduced to 5-6%.Percutaneous coronary intervention is the preferred treatment method for acute myocardial infarction recommended by the guidelines,saving the survival of myocardium,limiting the infarct size,and greatly reducing the mortality of patients with myocardial infarction.The survival rate of patients with acute myocardial infarction undergoing revascularization is improved,however,the incidence of heart failure after myocardial infarction is increased due to myocardial injury and ischemiareperfusion injury.The incidence of acute heart failure in patients with acute myocardial infarction undergoing revascularization is as high as 28%.Although the treatment of heart failure has made great progress in the past few decades,research has confirmed that heart failure is still an independent risk factor for short-term and long-term death of patients with myocardial infarction.Therefore,there is an urgent need to clarify the molecular mechanism of the development of heart failure after myocardial infarction,to find new treatment methods for heart failure,and to improve the prognosis of patients with heart failure after myocardial infarction.Under physiological conditions,90% of the heart's ATP is produced by mitochondrial oxidative phosphorylation using fatty acids as substrates.When mitochondrial function is restricted,it is produced by anaerobic glycolysis in the cell fluid.Cardiac metabolism can be divided into three parts: cell membrane absorption and cytoplasmic activation,mitochondrial oxidation and entry into the tricarboxylic acid cycle(TCA),and finally electron transfer and redox synthesis of ATP through the electron chain and ATP synthase.To maintain ATP production,the heart can metabolize a series of substrates,including fatty acids,sugars,ketone bodies,lactic acid,and amino acids.This equilibrium state of substrate metabolism can vary acutely or chronically depending on plasma substrate concentration,hormone levels,oxygen utilization,workload,and disease state.After myocardial infarction,due to myocardial ischemia,left ventricular hypertrophy and heart failure,the heart's internal and external influences have changed the choice and utilization of substrates,so that the heart has undergone significant metabolic changes,called "metabolic remodeling".This metabolic remodeling is believed to be an adaptive compensatory response,but it develops into an adverse reaction,which ultimately damages the energy metabolism of the heart and affects the contraction of the heart.During heart failure,fatty acid intake and oxidation are reduced,and glucose metabolism is increased.These changes are closely related to the left ventricular end-diastolic diameter and mass.In autopsy of patients with heart failure,it was found that the protein was reduced,and the mRNA expression of key enzymes for fatty acid transport and ? oxidation was reduced.Myocardial biopsy of patients with dilated cardiomyopathy was found to have increased glucose uptake and metabolism.The above research shows that cardiac metabolic remodeling is of great significance to the occurrence and progress of heart failure.At the same time,the research also found that improving the use of fatty acids and sugar is considered an effective method for treating heart failure.These findings provide us with a new view that improving the metabolic defects of myocardial cells during heart failure may be an effective method of treating heart failure.Therefore,in recent years,people have begun to explore the pathogenesis of heart failure by studying the changes of small molecule metabolite levels in order to discover new targets for heart failure treatment.Metabolomics systematically analyzes the content of small molecule metabolites in biological samples through high-throughput sequencing technology.Metabolomics is an emerging omics technology formed by the intersection of analytical chemistry,biochemistry and bioinformatics.As downstream products of genes,transcription,and proteins,the changes of metabolites can most accurately reflect the pathological changes in the disease process.Therefore,metabolomics can provide new methods for exploring the pathophysiological mechanism of diseases,and has become a hot spot in medical research.Amino acids are important nutrients for the survival and growth of cells,and they are also important substrates for energy and biosynthesis in cells.Studies have confirmed that myocardial infarction and heart failure can lead to abnormal metabolism of amino acids such as branched chain amino acids,taurine or glutamine.Abnormal metabolism of amino acids,such as branched-chain amino acids,can activate the mammalian rapamycin target protein signaling pathway(mTOR),accelerate myocardial remodeling,and lead to heart failure after myocardial infarction.Therefore,we analyzed the differences between plasma amino acid metabolites in patients with heart failure after myocardial infarction and patients with non-heart failure after myocardial infarction by liquid chromatography tandem mass spectrometry metabolomic method,and the most significant differences in metabolite branches were determined by cell experiments.Chain amino acids have been studied on the pathological mechanism of heart failure after myocardial infarction.This study explained the changes in plasma amino acid metabolism profiles of heart failure after myocardial infarction,discovered disease-related metabolic markers,and studied and explored the pathophysiological mechanism of heart failure after myocardial infarction.It is expected that metabolomic technology will provide new research ideas for the pathogenesis of heart failure after myocardial infarction,discover new disease prognostic markers and therapeutic targets,and improve the prognosis of patients with myocardial infarction.Aim:1.Discover abnormalities of amino acid metabolism during heart failure after revascularization in patients with acute myocardial infarction;2.Discover abnormalities of amino acid metabolites during heart failure worsening and progression after myocardial infarction;3.Explain the pathological mechanism of related metabolic changes in cardiovascular disease at the cellular level.Method:First,select patients who received adverse cardiovascular events after revascularization in patients with acute myocardial infarction and no adverse events,use mass spectrometry to detect the level of amino acid metabolites in plasma,and statistically find that patients with acute myocardial infarction are in hospital Metabolites related to adverse cardiovascular events;then we performed mass spectrometry of amino acids in plasma of patients with acute myocardial infarction and heart failure,and determined independent predictors related to the occurrence of end events by methods such as survival analysis,which were later found after myocardial infarction Metabolites related to the progression and deterioration of heart failure;finally we treated human umbilical vein endothelial cells with different concentrations of branched chain amino acids to observe the effects of branched chain amino acids on cell proliferation and apoptosis.Result:Principal component analysis showed that factors with branched-chain amino acid metabolites as the main component increased the risk of adverse events.Adding branched-chain amino acids to the GRACE score increased the consistency C value from 0.702 to 0.814(p<0.001),and the net weight classification index was 0.729.For patients with heart failure after myocardial infarction,multiple risk regression analysis showed that branched-chain amino acid levels were independent predictors of longterm adverse cardiovascular events in patients with myocardial infarction and heart failure.In the mechanism exploration,we found that with the increase of the concentration of branched chain amino acids,the proliferation of human umbilical vein endothelial cells gradually decreased,and the treatment of branched chain amino acids affected the expression of apoptotic factors.Conclusion:Plasma branched-chain amino acid levels in patients with acute myocardial infarction after revascularization are associated with adverse cardiovascular events occurring in the hospital,and plasma myocardial infarction patients with heart failure have plasma branched-chain amino acid levels associated with long-term adverse cardiovascular events.Risk-related,branched-chain amino acids inhibit cell proliferation of human umbilical vein endothelial cells and promote apoptosis. |
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