| Background:At present,coronary heart disease is still one of the diseases with the highest mortality and growing incidence in China.Early screening,diagnosis and treatment of coronary heart disease are accepted to be the most effective approaches to reducing the mortality of patients with this disease.Coronary angiography is the gold standard for the diagnosis of coronary heart disease.However,this technique is invasive for diagnosis,with the possibility of complications such as bleeding,acute vascular dissection,and contrast-induced nephropathy.Moreover,its application is restricted by personnel,equipment,location and other conditions,making it difficult for grassroots hospitals to carry out.Therefore,it highlights the significance of accurate,noninvasive,and simple methods for evaluating coronary artery lesions in clinical diagnosis and screening.As a new and effective risk assessment tool for cardiovascular diseases,the noninvasive cardiovascular function tester can assess cardiac hemodynamics,subendocardial perfusion,etc.Its parameter,i.e.,subendocardial viability ratio(SEVR),has been reported to be associated with subendocardial perfusion and coronary blood flow reserve.While it remains to be further clarified whether the noninvasive noninvasive cardiovascular function tester can be used for early screening of coronary heart disease and evaluating the recovery of myocardial perfusion after coronary artery stent implantation.Objective:The present study was performed to explore the application of related parameters of noninvasive cardiovascular function testing in assessing the severity of coronary artery lesions and myocardial perfusion recovery after coronary artery stent implantation.Method:A retrospective analysis was conducted by including 88 patients undergoing coronary angiography at Qilu Hospital of Shandong University from 2021 to 2023.1.General data and hematological test results of the enrolled patients were recorded through the electronic medical record system of this hospital.2.The cardiovascular function of patients was detected by using a non-invasive cardiovascular function tester before and after angiography,and the following related indicators were recorded,including the hemodynamic parameters of the central artery,pulse-wave conduction velocity,SEVR,etc.3.The coronary angiography results of patients after admission were collected to statistically analyze the degree of coronary artery stenosis.Meanwhile,based on the calculation of the coronary artery Gensini score,the enrolled patients were divided into the non-severe coronary artery lesion group(Gensini score:0-25.5 points)and severe coronary artery lesion group(Gensini score:>25.5 points)to compare changes in the above indicators.Simultaneously,independent influential factors of coronary artery lesion severity were assessed by using binary Logistic regression analysis.4.According to the condition of stent placement observed during coronary angiography,these patients were further divided into the stent group and non-stent group.Subsequently,based on the specific number of coronary stents implanted,patients in the stent group were further divided into specific stent groups(1 stent,2 stents,3 stents)to compare changes in various indicators among groups.Results:1.A total of 88 patients(mean age of 64.06±8.80 years)were included in this study,including 46 patients in the severe coronary artery lesion group and 42 cases in the non-severe coronary artery lesion group;39 cases in the stent group and 43 cases in the non-stent group,respectively.2.Comparison between the severe coronary artery lesion group and non-severe coronary artery lesion group:(1)There was an increased proportion in the severe coronary artery lesion group when compared to that in non-severe coronary artery lesion group(P<0.05).(2)In terms of hematological indexes,the severe coronary artery lesion group showed significantly higher levels in indicators of glycosylated hemoglobin,amino-terminal pro-brain natriuretic peptide,blood glucose,creatine kinase MB isoenzyme(CK-MB),troponin I,and lactate dehydrogenase(P<0.05);but High density lipoprotein cholesterol(HDL-C)obviously lower high-density lipoprotein(P<0.05)than those in non-severe coronary artery lesion group.(3)As for peripheral and central arterial pressures,the severe coronary artery lesion group had significantly increased brachial pulse pressure difference,central aortic systolic pressure,and central aortic pressure difference than those in non-severe coronary artery lesion group(P<0.05).(4)In related parameters of noninvasive cardiovascular function testing,the severe coronary artery lesion group revealed significantly lower SEVR(P<0.05);but obviously higher PWV(P<0.05)than those in non-severe coronary artery lesion group.(5)According to the results of correlation analysis,the severity of coronary artery lesion showed positive correlations with age(p=0.282,P<0.05),statin medication history(p=0.314,P<0.05).Gensini scores also had positive correlations with NT-ProBNP(p=0.3,P<0.05),glycosylated hemoglobin(p=0.328,P<0.05),homocysteine(p=0.249,P<0.05),free fatty acid(p=0.225,P<0.05),CTnI(p=0.368,P<0.05),and PWV(p=0.245,P<0.05);while exhibited negative correlations with high-density lipoprotein(p=-0.269,P<0.05)and SEVR(p=-0.213,P<0.05).(6)Binary Logistic regression analysis revealed that smoking history,CK-MB were risk factors for the severity of coronary artery lesions.High-density lipoprotein,SEVR were protective factors for the severity of coronary artery lesions.3.Comparison between the stent group and non-stent group:(1)There was no significant difference in gender,age,body mass index(BMI),hypertension history,diabetes history,smoking history and drinking history between the stent group and the non-stent group(P>0.05).(2)Among hematological indexes,CTnI in the stent group was significantly higher than that in the non-stent group(P<0.05).(3)Among related parameters of noninvasive cardiovascular function testing,the stent group showed significantly lower SEVR and PWV before and after angiography than those in the non-stent group,with a statistically significant difference(P<0.05).(4)Correlation analysis showed that the presence or absence of stent placement was negatively correlated with SEVR after angiography(r=-0.257,P<0.05),and positively correlated with △SEVR(r=0.272,P<0.05)and △PWV(r=0.264,P<0.05).4.Comparison in the number of stents placed and related parameters of noninvasive cardiovascular function testing(1)△SEVR increased significantly with the increase in the number of coronary stents(P<0.05).(2)Linear regression analysis showed that the number of stents placed was an independent risk factor affecting the level of △SEVR(P<0.05).Conclusion:1.The severity of coronary artery lesions is negatively correlated with SEVR.Subjects with more severe coronary artery lesions may have lower SEVR.At the same time,the severity of coronary artery lesions is Positively correlated with PWV.Subjects with more severe coronary artery lesions may have higher PWV.SEVR and PWV may be a novel noninvasive indicator for predicting the severity of coronary artery lesions.2.SEVR may contribute to assessing the recovery of myocardial perfusion after coronary artery stent implantation.3.Central arterial pressure can better reflect the extent of coronary artery lesions than peripheral arterial pressure.Background:Adenosine 5 ’-monophosphate(AMP)-activated protein kinase(AMPK)is the key regulator of cardiac energy metabolism and plays a significant part in the regulation of glucose and lipid metabolism.β-hydroxybutyric acid is an intermediate of fatty acid oxidation and the main form of ketone body,Lysine β-hydroxybutyrylation(Kbhb)is a novel posttranslational protein modification that is mediated by β-hydroxybutyric acid.It can assist the body in swiftly adjusting to and adapting to the metabolic changes brought on by the absence of an energy source.However,it is unknown if Kbhb influences the onset and progression of heart disease.Objective:Based on proteomics and β-hydroxybutanylation modification omics,to explore whether AMPK is concerned with controlling Kbhb of downstream substrates,thereby affecting cardiac phenotype and cardiac function changes,and to investigate key molecules associated with energy metabolism,providing new ideas for the prevention and treatment of diseases associated with abnormal cardiac energy metabolism.Methods:1.The genotype and phenotype of AMPKa2 mice were determined using PCR and Western Blot.2.Animal grouping:C57BL/6J wild type mice(n=10)and C57BL/6J AMPKα2 knockout mice(n=10).3.Treatment of animals:general mouse circumstances,including activity,nutrition,and mental state,were observed.We measured the mice’s body weight and grip strength at three months old.Echocardiography was used to evaluate cardiac function,especially the Left ventricular ejection fraction(LVEF),The Left ventricular fractional shortening(FS),the early diastolic mitral flow velocities(E)/the late diastolic mitral flow velocities(A)and the early diastolic mitral annulus velocities(E’)/the late diastolic mitral annulus velocities(A’).After mice were sacrificed,the serum levels of β-hydroxybutyric acid,free fatty acids,total cholesterol,and triglycerides were assessed.Mouse cardiac tissues were fixed and cryopreserved.4.Histopathological examination:hematoxylin-eosin staining(HE)was used to observe the structural changes of myocardium in the two groups.Transmission electron microscopy was used to observe the changes of cardiac ultrastructure.5.The overall amount of Kbhb modification was determined using Western Blot(WB)in the hearts of AMPKa2 knockout mice and young wild mice.6.Proteomics:The frozen heart tissues were analyzed by protein extraction,liquid chromatography-secondary mass spectrometry and bioinformatics.The differential proteins were searched for and their functions were analyzed.7.Kbhb modified omics:The frozen heart tissues were analyzed by protein extraction,liquid chromatography-secondary mass spectrometry and bioinformatics.The function of various Kbhb proteins was examined using bioinformatics analysis,which included protein annotation,GO analysis,and KEGG pathway analysis.Result:1.AMPKα2 did not elicit significant changes in appearance,BW,grip and HW.2.In the wild type group,the color of myocardium was uniform,the morphology was consistent,and the boundaries were clear.A few cardiac cell nucleus in the AMPKα2 knockout mice had swollen,along with the loose cytoplasm.The ultrastructure of myocardial cells showed,the wild type group,the myocardium mitochondria,round or oval shape,were arranged orderly,and the cristae in the whole mitochondrial cavity were dense and regularly distributed However,compared to the wild type group,the mitochondria of AMPKa2 knockout mice were distributed randomly,and the mitochondrial crest flattened.3.After AMPKa2 knockout,an apparent decrease in the LV diastolic functional parameter,such as E/A was observed.These results indicate that AMPKα2 knockout slightly impairs ventricular diastolic function.4.A total of 3659 proteins were quantified in AMPKa2 knockout and wild type mice.Finally,522 differential proteins were obtained by defining the truncation value as 1.5-fold.Among,these,57%(299/522)and 43%(223/522)were upregulated and downregulated differential proteins after AMPKa2 knockout.The complement and coagulation cascades and Staphylococcus aureus infection were significant in the KEGG pathway analysis for differential proteins.5.WB analysis confirmed that AMPKα2 knockout significantly reduces the overall Kbhb level in the heart.6.A 1.5-fold change resulted in 244 differential Kbhb sites of 142 proteins.Subsequently,140 differential Kbhb sites of 84 proteins were downregulated,while 104 differential Kbhb sites of 70 proteins were upregulated after AMPKa2 knockout.The subcellular localization of all differentially Kbhb proteins showed that most of the differential Kbhb proteins were located in the mitochondria(50/35.46%).Further research showed that prominent downregulated Kbhbmodified sites were associated with fatty acid metabolism and TCA cycle pathways.Conclusion:1.The general condition(appearance,body weight,grip strength,and heart weight)was unaltered by AMPKa2 knockout,but it altered the normal ultrastructure of the myocardium,causing the flattening and removal of mitochondrial cristas.2.After AMPKα2 knockout,an apparent decrease in the LV diastolic functional parameter,such as E/A was observed.These results indicate that AK slightly impairs ventricular diastolic function.3.AMPKa2 knockout significantly reduces the overall Kbhb level in the heart.AMPKa2 may regulate energy metabolism-related pathways by modifying protein Kbhb. |
PDF Full Text Request