| BackgroundAcute heart failure(AHF)is mainly caused by acute exacerbation of chronic heart failure(CHF),acute myocardial injury and necrosis,and acute hemodynamic disorder.It has the characteristics of acute onset,rapid progress,high mortality,and often endangers life.According to China heart failure diagnosis and treatment guidelines 2018,the in-hospital mortality of AHF is 3%,the readmission rate of 6 months is about 50%,and the 5-year mortality is about 60%.There have been many studies on the occurrence,development,treatment and prognosis of AHF around the world.The main inducing factor of AHF is acute coronary syndrome(ACS),both of which often exist at the same time.More than half of the hospitalized AHF patients have a history of coronary artery disease,15-28%of ACS patients have symptoms and signs of AHF,and even a considerable number of ACS patients occur AHF during hospitalization.Under normal conditions,the energy of myocardial metabolism is mainly provided by the oxidation of fatty acid,the metabolism of glucose,pyruvate,amino acid and ketone body is used as auxiliary energy.But when heart failure(HF)occurs,hypoxia makes the ability of uptake and oxidation of substrate and the utilization rate of fatty acid of the failing heart reduced sharply.The failing heart find that the efficiency of using glucose to produce ATP is higher than fatty acid oxidation,then the main process of energy supply gradually changes to glucose oxidation to ensure the operation of the failing heart.However,this change can only temporarily alleviate the lack of energy supply,myocardial and even systemic metabolic changes will occur if it continue this way and finally resulting in further energy metabolism disorders,aggravating the progress of the disease and becoming a complex clinical syndrome eventually,not only seriously affecting the quality of life,but also bringing various complications and huge burden of family and society.Metabolomics refers to the comprehensive detection of endogenous metabolites.Metabolomics focuses on small molecular metabolites which are the material basis for the body to complete various cellular processes and describes the role of various metabolites and metabolic pathways in the process of disease occurrence and development by the systematic research on small molecule metabolites.It is one of the most rapidly developing subjects at present.Metabolomics magnifies the changes in genomics and proteomics by focuses on small molecular metabolites and is more accurately approximates the healthy or disease phenotypes of organisms.There are few studies focus on metabolic changes of AHF patients by metabolomics around the world.Metabolomics has already become an important tool to understand the pathophysiology of cardiovascular disease,which is helpful to find out the role of metabolites or metabolic pathways in the progress of the disease.The metabolic state of the heart can be partly reflected in the metabolites such as plasma and urine in consideration of the detection of myocardial tissue is difficult to achieve.In order to further understand the metabolic characteristics of AHF caused by ischemia,to explore the metabolic target,and to clarify the myocardial energy metabolism under the condition of ischemia,this study took ACS patients with AHF(ACS-AHF)as the research object and used metabolomics to analyze the metabolic changes of ACS-AHF,analyzed the differential metabolites so as to provide new ideas for the reasonable treatment.Objectives1.To explore the changes of metabolites and metabolic pathways of ACS-AHF.2.To analyze the heart energy supply of ACS-AHF.3.To find the differential metabolites between the two groups and explore their therapeutic value for ACS-AHF.Subjects and MethodsA total of 43 patients with ACS were selected for the study,including 24 patients without AHF in the control group and 19 in the ACS-AHF group.Physical examination,blood pressure,heart rate were carried out for all subjects.Previous history,medication history,allergy history were inquired.All the subjects fasted for 12-14 hours overnight on the day of admission.Fasting venous blood was collected to measure Na+,K+,creatinine(Cr),blood urea nitrogen(BUN),hemoglobin(Hb),triglyceride(TG),total cholesterol(TC),low-density lipoprotein(LDL),high density lipoprotein(HDL)in the morning of the next day.The plasma was frozen and stored at-80? after centrifugation.50%methanol buffer was used to extract metabolites.Prepare mixed quality control samples.Ultra high performance liquid chromatography(UPLC)system was used for chromatographic separation and then the metabolites eluted from the column were detected by high-resolution tandem mass spectrometer for qualitative and quantitative analysis.Results1.There was no significant difference between control and ACS-AHF group in gender,smoking history,drinking history,hypertension history,heart rate,respiratory rate,rate of neck vein distention,rate of angiotensin converting enzyme inhibitors(ACEI)/angiotensin receptor blocker(ARB)using,rate of ? receptor blocker using.Age,heart history ratio,lower extremity edema ratio,diuretic use rate,Cr level were significantly higher(P<0.05)in patients of ACS-AHF group compared with control,moist crackles ratio was also significantly higher(P<0.001).Systolic blood pressure,Na+,TG and TC level were significantly decreased(P<0.05).2.A total of 650 secondary identifications were obtained from the metabolomics analysis of plasma and involved in many kinds,of which more than 50%were lipids and lipid-like molecules.3.Principal component analysis(PCA)model and orthogonal partial least squares discrimination analysis(OPLS-DA)model showed that the observed variables of plasma metabolites are highly consistently within each group,and there were a distinct trend of differentiation and clustering between the two groups,which means there were significant metabolic differences.4.27 metabolites which had significant difference between the two groups were obtained by independent sample t-test.Phenol,acylcarnitine 14:2,oxyphenbutazone,(3E,7E)-4,8,12-trimethyl-1,3,7,11-tridecatetraene,acylcarnitine 14:3,lauroyl-L-carnitine,acylcarnitine 16:2,acylcarnitine 16:3,acylcarnitine 10:1,hexanoyl-L-carnitine,palmitoleic acid,acylcarnitine 12:1,cannabidiolic acid,octanoylcarnitine,palmitelaidic acid,acylcarnitine 15:1,acylcarnitine 14:0,N-isobutyrylglycine,acylcarnitine 16:4,acylcarnitine 18:4,acylcarnitine 16:1,phenylbutazone,acylcarnitine 14:1 were significantly increased in ACS-AHF group compared with control.1-methylene-5?-androstan-3?-ol-1 7-one,decanoyl-L-carnitine,?-hydroxyisobutyric acid,4-hydroxybenzoic acid were significantly decreased.5.Kyoto encyclopedia of genes and genomes(KEGG)database analysis showed that the differential metabolites were widely found in glucose metabolism,lipid metabolism,amino acid metabolism,ketone metabolism and other metabolic pathways.Fatty acid metabolism,glycolysis and ketone metabolism were enhanced,glucose oxidation was weakened,and fatty acid metabolism pathway changed most significantly.Conclusion1.ACS-AHF caused metabolic disorder in the whole body.All metabolic pathways changed a lot and fatty acid metabolism changed most significantly.2.Fatty acids oxidation increased and glucose oxidation gradually transformed into glycolysis to meet the myocardial energy supply after the initial phase of ACS-AHF.3.27 differential metabolites of ACS-AHF were found.Palmitoleic acid,palmitelaidic acid,?-hydroxyisobutyric acid and 4-hydroxybenzoic are potential therapeutic targets of ACS-AHF. |
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