| Objective:This study aimed to explore the influencing factors of the upregulation of serum intercellular adhesion molecule-1(ICAM-1)and vascular cell adhesion molecule-1(VCAM-1),then further explore the serum metabolic change related to the upregulation of serum ICAM-1 and VCAM-1,increasing an understanding of the mechanism of early pathological changes of vascular endothelial inflammation from a metabolic perspective.Methods:This study is a cross-sectional investigation design.A convenience sampling method was used to recruit residents in Rongan County and Rongshui County,Guangxi.The survey method was mainly composed of three parts:(1)Self-reported questionnaires was used to collect the general sociodemographic information of the research subjects,including smoking history,current disease and recent drug use;(2)The height,weight,blood pressure were measured during the physical examinations;(3)Blood samples of the research subjects were collected for measuring the concentrations of serum soluble ICAM-1,serum soluble VCAM-1,serum glucose,serum total cholesterol(TC),serum high density lipoprotein cholesterol(HDL-c),serum low density lipoprotein cholesterol(LDL-c),serum triglyceride(TG),serum C-reactive protein(CRP)and other blood biochemical indicators.A total of 1149 subjects were recruited for this study,and the analysis included two parts.According to the inclusion and exclusion criteria,497subjects were selected from 1,149 subjects for the analysis of first part,which contents were as follows:(1)Described the basic characteristics of the overall research objects;(2)Described the serum ICAM-1 concentration and serum VCAM-1 concentration of the research objects at different characteristic;(3)The study subjects were divided into the serum ICAM-1 high-level group and serum ICAM-1 low-level group,serum VCAM-1 high-level group and serum VCAM-1 low-level group according to the median of serum ICAM-1concentration and the median of VCAM-1 concentration respectively.Simple Logistic regression and multiple Logistic regression analysis were used to explore the correlation factors of serum ICAM-1 high-level concentration and serum VCAM-1 high-level concentration respectively.In the second part of the analysis,99 subjects were selected from 497subjects of the first part analysis for measuring serum metabolites.The 99subjects were divided into the serum ICAM-1 high-level group and the serum ICAM-1 low-level group according to the median concentration of serum ICAM-1.We selected 35 individuals from the serum ICAM-1 high-level group and the serum ICAM-1 low-level group respectively based on the social demographic characteristics,smoking status,physical activity,BMI and blood biochemical indicators balanced between two groups,then conduct metabolomics analysis used the serum ICAM-1 low-level group as control.In addition,according to the same principle,35 individuals in the serum VCAM-1high-level group and 37 individuals in the serum VCAM-1 low-level group were selected for serum metabolic analysis used the serum VCAM-1 low-level group as the control.The above analysis of metabolic changes was based on the GC-TOF-MS platform to detect metabolites in the serum of the study subjects,and the analysis content included:(1)Performed principal component analysis(PCA);(2)Orthogonal partial least squares-discriminant analysis(OPLS-DA)and student t test to identify differential metabolites between the two comparison groups;(3)The differential metabolic pathways were analyzed based on the differential metabolites of the two comparison groups respectively.Results:PartⅠ1.Among the 497 subjects,the average age was 55.8±0.5 years,182 males(36.6%)and 315 females(63.4%).The median concentration of serum ICAM-1was 72.0 ng/m L(IQR:60.9 ng/m L),the median concentration of serum VCAM-1 was 359.5 ng/m L(IQR:163.4 ng/m L).The concentration of serum ICAM-1 between subjects with different diabetes status significantly difference(P<0.05).Serum VCAM-1 concentrations of subjects with different ages,education status,BMI levels,serum lipid levels were significantly difference(P<0.05).2.Multiple Logistic regression analysis showed that after adjustment for all confounding factors,BMI≥24 kg/m~2,dyslipidemia were positively correlated to serum ICAM-1 high-level concentration(P<0.05);BMI≥24 kg/m~2,dyslipidemia,estimate glomerular filtration rate(eGFR)<90 m L/min/1.73 m~2,hypertension were still negative correlated to serum VCAM-1 high-level concentration(P<0.05).PartⅡ1.The mean age of 35 subjects in serum ICAM-1 high-level group was56.0±1.3 years and the median serum ICAM-1 concentration was 105.8 ng/m L(IQR:78.0 ng/m L);the mean age of 35 subjects in serum ICAM-1 low-level group was 58.3±1.1 years and the median serum ICAM-1 concentration was41.6 ng/m L(IQR:13.6 ng/m L).The mean age of 35 subjects in serum VCAM-1high-level group was 57.9±1.1 years and the median serum VCAM-1concentration was 490.9 ng/m L(IQR:105.0 ng/m L);the mean age of 37subjects in serum VCAM-1 low-level group was 55.2±1.1 years and the median serum VCAM-1 concentration was 328.0 ng/m L(IQR:88.0 ng/m L).There was no significant difference in age,gender,ethnicity and blood biochemical indexes between the serum ICAM-1 high-level group and low-level group,and between the serum VCAM-1 high-level group and low-level group.2.Compared with serum ICAM-1 low-level group,metabolic changes analysis showed that the contents of 9 metabolites including palmitic acid,stearic acid,palmitoleic acid,methyl phosphate,pipecolinic acid,2-Ketovaleric acid,phthalic acid,valine,O-methylthreonine increased(Fold change>1)in serum ICAM-1 high-level group.Compared with serum VCAM-1 low-level group,the contents of 9 metabolites including ornithine,tryptophan,taurine,methylmalonic acid,oxamide,beta-alanine,thymidine,glutamic acid,N-Acetyl-D-galactosamine decreased(Fold change<1)in VCAM-1 high-level group.3.Metabolic Pathway analysis showed that there were no significant disturbed metabolic pathways in the serum ICAM-1 high-level group compared with the serum ICAM-1 low-level group(P>0.05 or Impact=0).Compared with the serum VCAM-1 low-level group,6 metabolic pathways were disturbed(P<0.05,Impact>0)in the serum VCAM-1 high-level group,which were arginine biosynthesis,glutathione metabolism,arginine and proline metabolism,pyrimidine metabolism,D-Glutamine and D-glutamate metabolism,taurine and hypotaurine metabolism.Conclusion:1.The influencing factors of the serum soluble ICAM-1 high-level concentration and serum soluble VCAM-1 high-level concentration were different.BMI≥24 kg/m~2and dyslipidemia increased the risk of the serum ICAM-1 high-level concentration.BMI≥24 kg/m~2,dyslipidemia,eGFR<90m L/min/1.73 m~2,and hypertension reduced the risk of serum VCAM-1high-level concentration.2.The metabolic changes of upregulation of serum soluble ICAM-1 level altered to increased contents of palmitic acid and octadecanoic acid,which may be related to the pro-inflammatory status in vivo.In addition,the decreased of maleic acid content may be related to the inhibition of the tricarboxylic acid cycle.3.The upregulation of serum soluble VCAM-1 levels altered to decreased levels of ornithine and glutamate,as well as to involve changes in arginine biosynthesis and glutathione metabolic pathways,which may be associated with decreased antioxidant and anti-inflammatory capacity in vivo as well as decreased vascular endothelial nitric oxide(NO)synthesis. |
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