New circulating metabolites might allow early diagnosis of cardiovascular disease. A team of scientists from Uppsala University, Karolinska Institutet and Colorado State University have identified novel lipid-derived molecules associated with future coronary heart disease events. The study published in the journal PLOS Genetics has examined the metabolic profile of blood samples from more than 3,600 individuals that have been followed-up for up to 10 years.
Professor Erik Ingelsson and graduate student Andrea Ganna have used novel biochemical and bioinformatics approaches to identify small molecules that are the intermediate – or end-products of metabolism. This approach, called metabolomics, has identified two lipid metabolites, lysophosphatidylcholine and sphingomyelin that reduced the risk of developing coronary heart disease in three Swedish population studies. Another lipid metabolite, monoglyceride, was instead associated with increased risk of coronary heart disease.
One of the strengths of this study was that all participants were profiled for both metabolites and genetic variants. Some of the metabolites showed strong association with genetic variants previously associated with coronary heart disease supporting a common underlying molecular mechanism. Another strength was that the results were replicated in studies with different follow-up time, blood partition, age and sex distribution, increasing the generalizability of the findings.
This study shows the advantages of integrating different – omics technologies in large epidemiological studies. The blood lipid metabolites identified could be useful in prediction of future cardiovascular disease. In vivo experiments are ongoing to investigate the potential causal role of these metabolites in the development of cardiovascular disease. If confirmed, these findings could also point to new therapeutic targets.
Large-scale Metabolomic Profiling Identifies Novel Biomarkers for Incident Coronary Heart Disease, Ganna A, Salihovic S, Sundstro¨m J, Broeckling CD, Hedman AK, et al.,PLoS Genetics, doi:10.1371/journal.pgen.1004801, published 11 December 2014.
This study was supported by grants from Knut och Alice Wallenberg Foundation (Wallenberg Academy Fellow), European Research Council (ERC-2013- StG; grant no. 335395), Swedish Diabetes Foundation, Swedish Heart-Lung Foundation (grant no. 20120197), and Swedish Research Council (grant no. 2012-1397). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
The authors have declared that no competing interests exist.