Jowy Yi Hoong Seah1,2, Wee Siong Chew3, Federico Torta4,5, Chin Meng Khoo6, Markus R Wenk4,5,7, Deron R Herr3,8, Hyungwon Choi9,6,10, E Shyong Tai9,6,11, Rob M van Dam12,13,14. 1. Saw Swee Hock School of Public Health, National University of Singapore (NUS), 12 Science Drive 2, #10-01, Singapore, 117549, Singapore. ephsyh@nus.edu.sg. 2. NUS Graduate School for Integrative Sciences and Engineering, NUS, Singapore, 119077, Singapore. ephsyh@nus.edu.sg. 3. Department of Pharmacology, Yong Loo Lin School of Medicine, NUS, Singapore, 117600, Singapore. 4. Department of Biochemistry, Yong Loo Lin School of Medicine, NUS, Singapore, 117596, Singapore. 5. Singapore Lipidomics Incubator, Life Sciences Institute, NUS, Singapore, 117456, Singapore. 6. Department of Medicine, Yong Loo Lin School of Medicine, NUS and National University Health System, Singapore, 119228, Singapore. 7. Department of Biological Sciences, Faculty of Science, NUS, Singapore, 117558, Singapore. 8. Department of Biology, San Diego State University, San Diego, CA, 92182, USA. 9. Saw Swee Hock School of Public Health, National University of Singapore (NUS), 12 Science Drive 2, #10-01, Singapore, 117549, Singapore. 10. Institute of Molecular and Cell Biology, Agency for Science, Technology, and Research, Singapore, 138673, Singapore. 11. Duke-NUS Graduate Medical School, Singapore, 169857, Singapore. 12. Saw Swee Hock School of Public Health, National University of Singapore (NUS), 12 Science Drive 2, #10-01, Singapore, 117549, Singapore. rob.van.dam@nus.edu.sg. 13. NUS Graduate School for Integrative Sciences and Engineering, NUS, Singapore, 119077, Singapore. rob.van.dam@nus.edu.sg. 14. Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, 02115, USA. rob.van.dam@nus.edu.sg.
Abstract
INTRODUCTION: Sphingolipids are a diverse class of lipids with various roles in cell functions and subclasses such as ceramides have been associated with cardiovascular diseases (CVD) in previous studies. OBJECTIVES: We aimed to measure molecularly-distinct sphingolipids via a large-scale lipidomic analysis and expand the literature to an Asian population. METHODS: We performed a lipidomics evaluation of 79 molecularly distinct sphingolipids in the plasma of 2627 ethnically-Chinese Singaporeans. RESULTS: During a mean follow-up of 12.9 years, we documented 152 cases of major CVD (non-fatal myocardial infarction, stroke and cardiovascular death). Total ceramide concentrations were not associated with CVD risk [hazard ratio (HR), 0.99; 95% CI 0.81-1.21], but higher circulating total monohexosylceramides (HR, 1.22; 95% CI 1.03, 1.45), total long-chain sphingolipids (C16-C18) (HR, 1.22; 95% CI 1.02, 1.45) and total 18:1 sphingolipids (HR, 1.21; 95% CI 1.01, 1.46) were associated with higher CVD risk after adjusting for conventional CVD risk factors. CONCLUSIONS: Our results do not support the hypothesis that higher ceramide concentrations are linked to higher CVD risk, but suggest that other classes of sphingolipids may affect CVD risk.
INTRODUCTION:Sphingolipids are a diverse class of lipids with various roles in cell functions and subclasses such as ceramides have been associated with cardiovascular diseases (CVD) in previous studies. OBJECTIVES: We aimed to measure molecularly-distinct sphingolipids via a large-scale lipidomic analysis and expand the literature to an Asian population. METHODS: We performed a lipidomics evaluation of 79 molecularly distinct sphingolipids in the plasma of 2627 ethnically-Chinese Singaporeans. RESULTS: During a mean follow-up of 12.9 years, we documented 152 cases of major CVD (non-fatal myocardial infarction, stroke and cardiovascular death). Total ceramide concentrations were not associated with CVD risk [hazard ratio (HR), 0.99; 95% CI 0.81-1.21], but higher circulating total monohexosylceramides (HR, 1.22; 95% CI 1.03, 1.45), total long-chain sphingolipids (C16-C18) (HR, 1.22; 95% CI 1.02, 1.45) and total 18:1 sphingolipids (HR, 1.21; 95% CI 1.01, 1.46) were associated with higher CVD risk after adjusting for conventional CVD risk factors. CONCLUSIONS: Our results do not support the hypothesis that higher ceramide concentrations are linked to higher CVD risk, but suggest that other classes of sphingolipids may affect CVD risk.
Authors: Peter McGranaghan; Jennifer A Kirwan; Mariel A Garcia-Rivera; Burkert Pieske; Frank Edelmann; Florian Blaschke; Sandeep Appunni; Anshul Saxena; Muni Rubens; Emir Veledar; Tobias Daniel Trippel Journal: Metabolites Date: 2021-09-14
Authors: Jowy Yi Hoong Seah; Wee Siong Chew; Federico Torta; Chin Meng Khoo; Markus R Wenk; Deron R Herr; E Shyong Tai; Rob M van Dam Journal: Metabolites Date: 2021-02-08
Authors: Nadja S Sieber-Ruckstuhl; Wai Kin Tham; Franziska Baumgartner; Jeremy John Selva; Markus R Wenk; Bo Burla; Felicitas S Boretti Journal: Metabolites Date: 2022-03-30