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Updated: Sep 24, 2025
On-Chip Endothelial Inflammatory Phenotyping
Published on: July 21, 2012
Metabolic profiling reveals the heterogeneity of vascular endothelial function phenotypes in individuals at extreme
Baoyu Mao1, Yanshan Yi1, Qiuyan Mo1
1Guangxi Colleges and Universities Key Laboratory of Prevention and Control of Highly Prevalent Diseases, Guangxi Medical University School of Public Health 22 Shuangyong Road Nanning 530021 China qazhong@gxmu.edu.cn.
Insights
Distinct serum metabolic profiles reveal varied vascular endothelial function in high-risk individuals. This research clarifies the heterogeneous pathogenesis of atherosclerotic cardiovascular disease (CVD) in asymptomatic populations.
Area of Science:
- Metabolomics
- Cardiovascular Disease Research
- Endothelial Function
Background:
- Vascular endothelial metabolism's role in atherosclerotic cardiovascular disease (CVD) pathogenesis is not fully understood, especially concerning differing endothelial function phenotypes.
- Heterogeneity in CVD pathogenesis limits effective early intervention strategies.
Purpose of the Study:
- To profile serum metabolic alterations in asymptomatic adults with varying vascular endothelial function phenotypes and extreme cardiovascular risk.
- To elucidate distinct metabolic patterns associated with normal, risk-promoting, risk-resistant, and vulnerable endothelial function.
Main Methods:
- Serum metabolic profiles were analyzed using gas chromatography time-of-flight/mass spectrometry.
- Multivariate statistical analyses were employed to compare metabolic profiles across different endothelial function groups.
- Individuals were categorized into normal endothelial function (NEF), cardiovascular risk-promoting endothelial function (PEF), cardiovascular risk-resistant endothelial function (REF), and vulnerable endothelial function (VEF) groups.
Main Results:
- Significant differences in serum metabolites were observed between groups, with 17 in PEF, 17 in REF, 22 in VEF, and 13 in CVD compared to NEF.
- Shared altered metabolic pathways between PEF and CVD groups included pyrimidine metabolism, starch/sucrose metabolism, aminoacyl-tRNA biosynthesis, arginine/proline metabolism, and d-glutamine/d-glutamate metabolism.
- Unique findings included increased galactose metabolism in REF and an elevated acetyl-CoA to CoA ratio in VEF.
Conclusions:
- Distinct metabolic signatures characterize heterogeneous vascular endothelial function in individuals at high cardiovascular risk.
- These findings enhance understanding of the pathogenic heterogeneity underlying early-stage CVD in asymptomatic populations.
- Metabolic profiling offers potential for identifying distinct CVD risk trajectories.
Abstract:
Maladapted vascular endothelial metabolism in the context of endothelial function differing in phenotype remains unknown, which limits our understanding of the heterogeneous pathogenesis of atherosclerotic cardiovascular disease (CVD). This study aimed to profile serum metabolic alterations of different vascular endothelial function phenotypes in asymptomatic adults at extreme cardiovascular risk. In addition to 12 CVD patients, 103 individuals free of CVD were categorized as having normal endothelial function (NEF) (n = 30), cardiovascular risk-promoting endothelial function (PEF) (n = 18), cardiovascular risk-resistant endothelial function (REF) (n = 25), and vulnerable endothelial function (VEF) (n = 30). Serum metabolic profiles were detected using gas chromatography time-of-flight/mass spectrometry and multivariate statistics. Compared to the NEF group, a total of 17, 17, 22, and 13 differential metabolites were identified in the PEF, REF, VEF, and CVD groups, respectively. Of the altered metabolic pathways, multiple pathways were consistent between the PEF and CVD groups, including pyrimidine metabolism, starch and sucrose metabolism, aminoacyl-tRNA biosynthesis, arginine and proline metabolism, and d-glutamine and d-glutamate metabolism. Notably, a relative increase in low-calorie sugar in galactose metabolism was exclusively found in the REF group, and a relative increase in the ratio of acetyl-CoA to CoA was suggested in the VEF group based on elevated butanoate metabolism and reduced pantothenate and CoA biosynthesis. Our findings clearly indicate distinct metabolic patterns across groups with heterogeneous vascular endothelial function in the context of extreme cardiovascular risk, and improve our understanding of the pathogenic heterogeneity of early CVD in asymptomatic populations.
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