Metabolomic Identification of a Novel Pathway of Blood Pressure Regulation Involving Hexadecanedioate

Menni, Cristina; Graham, Delyth; Kastenmüller, Gabi; Alharbi, Nora Hassan J.; Alsanosi, Safaa; McBride, Martin W.; Mangino, Massimo; Titcombe, Philip; Shin, So Youn; Psatha, Maria; Geisendorfer, Thomas; Huber, Anja; Peters, Annette; Wang-Sattler, Rui; Xu, Tao; Brosnan, M. Julia; Trimmer, Jeff K.; Reichel, Christian; Mohney, Robert P.; Soranzo, Nicole; Edwards, Mark H.; Cooper, Cyrus; Church, Alistair Colin; Suhre, Karsten; Gieger, Christian; Dominiczak, Anna F.; Spector, Tim D.; Padmanabhan, Sandosh; Valdes, Ana M.

doi:10.1161/hypertensionaha.115.05544

Cited by 96 publications

(94 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…41,42 Graessler et al 41 reported altered blood plasma levels of acylalkyl-phosphatidylcholines in hypertensive German men, relative to the control group of normotensive men. Notably, identified acylalkyl-phosphatidylcholines (C36:4, C36:5, C38:4-C38:6) were highly unsaturated, as the 3 identified phosphatidylcholines metabolites in this study which may be beneficial to enhance membrane fluidity.…”

Section: Discussionmentioning

confidence: 99%

“…However, none of the metabolites, reported by Graessler et al, 41 were associated with incident hypertension in this study, suggesting differences in metabolite composition of individuals with incident and prevalent hypertension. Recently, of 280 metabolites, 15 metabolites were identified by Menni et al 42 to be independently associated with BP. However, of identified metabolites, only hexadecanedioate, a dicarboxylic acid, showed concordant association with BP in 2 replication cohort (KORA and Hertfordshire).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Identification of Serum Metabolites Associated With Incident Hypertension in the European Prospective Investigation Into Cancer and Nutrition–Potsdam Study

et al. 2016

View full text Add to dashboard Cite

Essential hypertension is among the most important preclinical conditions of metabolic syndrome and affects nearly 1 billion people worldwide.1,2 The risk to develop essential hypertension seems to be a function of age, triggered by an unhealthy lifestyle with obesity, and physical inactivity as major risk factors.1 Furthermore, dyslipidemia, 3 inflammatory processes, 4 and oxidative stress 5 have been closely linked to this preclinical condition. Although many pathophysiological mechanisms of hypertension have been elucidated, knowledge is scarce about individual metabolic alterations promoting the development of essential hypertension in healthy subjects or subjects in early stages of this condition.Application of metabolomics can contribute to fill this gap and generate further insights into the pathogenesis of hypertension development. Metabolites represent intermediates and end products of cellular processes and are substantial for signaling, structuring of membranes, and catalytic activity. Metabolic alterations associated with development of hypertension, therefore, may be present years before hypertension diagnosis. Hence, investigating metabolic profiles in prospective cohorts is a promising opportunity to improve our knowledge of incident hypertension and to discover novel biomarkers that elucidate early changes in potential pathways.In the US cohort, of 204 metabolites, the metabolite 4-hydroxyhippurate and a metabolic sex steroids pattern were associated with incident hypertension. 6 Another US study using metabolic profiling revealed an association of diacylglycerols, in general, and of the 2 diacylglycerols 16:0/22:5 and 16:0/22:6, in particular, with blood pressure (BP) and incident hypertension. 7 However, to our knowledge, only a few prospective studies have used metabolic profiling to investigate metabolic alterations associated with incident hypertension, 6,7 and thus further studies are necessary to elucidate this promising approach.This study aimed to identify metabolites associated with incident hypertension using data of 127 serum metabolites (Biocrates AbsoluteIDQ p150) determined within the European Prospective Abstract-Metabolomics is a promising tool to gain new insights into early metabolic alterations preceding the development of hypertension in humans. We therefore aimed to identify metabolites associated with incident hypertension using measured data of serum metabolites of the European Prospective Investigation Into Cancer and Nutrition (EPIC)-Potsdam study. Targeted metabolic profiling was conducted on serum blood samples of a randomly drawn EPIC-Potsdam subcohort consisting of 135 cases and 981 noncases of incident hypertension, all of them being free of hypertension and not on antihypertensive therapy at the time of blood sampling. Mean follow-up was 9.9 years. A validated set of 127 metabolites was statistically analyzed with a random survival forest backward selection algorithm to identify predictive metabolites of incident hypertension taking into account important epidemiol...

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Identification of Serum Metabolites Associated With Incident Hypertension in the European Prospective Investigation Into Cancer and Nutrition–Potsdam Study

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Metabolomics is a new high-throughput technology that measures endogenous metabolites in cells, tissues and other biosamples such as blood, urine and saliva (15) . These metabolites provide a direct signature of the biochemical activities of the individual at a particular time, reflecting the metabolic effects of nutritional intake, physical activities and environmental exposures as well as the biological pathways associated with diet-related diseases including obesity, CVD and type 2 diabetes (16)(17)(18)(19) . Metabolites have been proven to be of use in nutritional research and novel dietary biomarkers within the metabolome have been identified (20)(21)(22)(23) .…”

Section: Metabolomicsmentioning

confidence: 99%

Lessons on dietary biomarkers from twin studies

Menni

2017

Proc. Nutr. Soc.

Self Cite

View full text Add to dashboard Cite

Metabolomic and microbiome profiling are promising tools to identify biomarkers of food intake and health status. The individual's genetic makeup plays a significant role on health, metabolism, gut microbes and diet and twin studies provide unique opportunities to untangle gene–environment effects on complex phenotypes. This brief review discusses the value of twin studies in nutrition research with a particular focus on metabolomics and the gut microbiome. Although, the twin model is a powerful tool to segregate the genetic component, to date, very few studies combine the twin design and metabolomics/microbiome in nutritional sciences. Moreover, since the individual's diet has a strong influence on the microbiome composition and the gut microbiome is modifiable (60 % of microbiome diversity is due to the environment), future studies should target the microbiome via dietary interventions.

show abstract

“…As yet there are, however, only limited data available that specifically address hypertension, in part because of the difficulties disentangling blood pressure from its consequences including target organ damage. Nevertheless, some metabolites such as hexadecanedioate have been found to be differentially regulated in hypertension [28] and the potential of proteomics to impact on cardiovascular health and disease has recently been defined [29]. In specific hypertensive conditions such as pre-eclampsia a wealth of proteomic and metabolomic data are available that provide some insights into the pathogenesis that could also inform our understanding of essential hypertension and other vascular diseases [30][31][32].…”

Section: Genetic Aspects and "Omics"mentioning

confidence: 99%

Use of Biomarkers in the Evaluation and Treatment of Hypertensive Patients

Currie

Delles

2016

Curr Hypertens Rep

View full text Add to dashboard Cite

The current definition of hypertension is based on blood pressure values, and blood pressure also drives treatment decisions, is the most important treatment monitoring tool and helps estimating risk of hypertension related organ damage. In an era of precision medicine additional biomarkers are needed in the diagnosis and management of patients with hypertension. In this review we outline the areas in which functional, imaging and circulating biomarkers could help in a more individualised definition of hypertension and associated risk. We will cover biomarkers for diagnosis; of pathophysiology and prediction of hypertension; response to treatment, organ damage; and to monitor treatment. A clear focus is on the vasculature, the heart and the kidneys, whereas we see a need to further develop biomarkers of cerebral function in order to diagnose cognition deficits and monitor changes in cognition in the future to support addressing the growing burden of hypertension associated vascular dementia.3

show abstract

Metabolomic Identification of a Novel Pathway of Blood Pressure Regulation Involving Hexadecanedioate

Abstract: Supplemental Digital Content is available in the text.

Cited by 96 publications

References 38 publications

Identification of Serum Metabolites Associated With Incident Hypertension in the European Prospective Investigation Into Cancer and Nutrition–Potsdam Study

Identification of Serum Metabolites Associated With Incident Hypertension in the European Prospective Investigation Into Cancer and Nutrition–Potsdam Study

Lessons on dietary biomarkers from twin studies

Use of Biomarkers in the Evaluation and Treatment of Hypertensive Patients

Contact Info

Product

Resources

About