Background Epidemiological and animal studies have associated systemic inflammation with blood pressure (BP). However, the mechanistic factors linking inflammation and BP remain unknown. Fatty acid–derived eicosanoids serve as mediators of inflammation and have been suggested to regulate renal vascular tone, peripheral resistance, renin‐angiotensin system, and endothelial function. We hypothesize that specific proinflammatory and anti‐inflammatory eicosanoids are linked with BP. Methods and Results We studied a population sample of 8099 FINRISK 2002 participants randomly drawn from the Finnish population register (53% women; mean age, 48±13 years) and, for external validation, a sample of 2859 FHS (Framingham Heart Study) Offspring study participants (55% women; mean age, 66±9 years). Using nontargeted liquid chromatography–mass spectrometry, we profiled 545 distinct high‐quality eicosanoids and related oxylipin mediators in plasma. Adjusting for conventional hypertension risk factors, we observed 187 (34%) metabolites that were significantly associated with systolic BP ( P <Bonferroni‐corrected threshold of 0.05/545). We used forward selection linear regression modeling in FINRISK to define a general formula for individual eicosanoid risk score. Individuals of the top risk score quartile in FINRISK had a 9.0 (95% CI, 8.0–10.1) mm Hg higher systolic BP compared with individuals in the lowest quartile in fully adjusted models. Observed metabolite associations were consistent across FINRISK and FHS. Conclusions Plasma eicosanoids demonstrate strong associations with BP in the general population. As eicosanoid compounds affect numerous physiological processes that are central to BP regulation, they may offer new insights about the pathogenesis of hypertension, as well as serve as potential targets for therapeutic intervention.

IntroductionPeptide markers of inflammation have been associated with the development of type 2 diabetes. The role of upstream, lipid-derived mediators of inflammation such as eicosanoids, remains less clear. The aim of this study was to examine whether eicosanoids are associated with incident type 2 diabetes.Research design & methodsIn the FINRISK (Finnish Cardiovascular Risk Study) 2002 study, a population-based sample of Finnish men and women aged 25–74 years, we used directed, non-targeted liquid chromatography-mass spectrometry to identify 545 eicosanoids and related oxylipins in the participants’ plasma samples (n=8292). We used multivariable-adjusted Cox regression to examine associations between eicosanoids and incident type 2 diabetes. The significant independent findings were replicated in the Framingham Heart Study (FHS, n=2886) and DIetary, Lifestyle and Genetic determinants of Obesity and Metabolic syndrome (DILGOM) 2007 (n=3905). Together, these three cohorts had 1070 cases of incident type 2 diabetes.ResultsIn the FINRISK 2002 cohort, 76 eicosanoids were associated individually with incident type 2 diabetes. We identified three eicosanoids independently associated with incident type 2 diabetes using stepwise Cox regression with forward selection and a Bonferroni-corrected inclusion threshold. A three-eicosanoid risk score produced an HR of 1.56 (95% CI 1.41 to 1.72) per 1 SD increment for risk of incident diabetes. The HR for comparing the top quartile with the lowest was 2.80 (95% CI 2.53 to 3.07). In the replication analyses, the three-eicosanoid risk score was significant in FHS (HR 1.24 (95% CI 1.10 to 1.39, p<0.001)) and directionally consistent in DILGOM (HR 1.12 (95% CI 0.99 to 1.27, p=0.07)). Meta-analysis of the three cohorts yielded a pooled HR of 1.31 (95% CI 1.05 to 1.56).ConclusionsPlasma eicosanoid profiles predict incident type 2 diabetes and the clearest signals replicate in three independent cohorts. Our findings give new information on the biology underlying type 2 diabetes and suggest opportunities for early identification of people at risk.

Astrobiology asks three fundamental questions as outlined by the NASA Astrobiology Roadmap: 1. How did Life begin and evolve?; Is there Life elsewhere in the Universe?; and, What is the future of Life on Earth? As we gain perspective on how Life on Earth arose and adapted to its many niches, we too gain insight into how a planet achieves habitability. Here on Earth, microbial Life has evolved to exist in a wide range of habitats from aquatic systems to deserts, the human body, and the International Space Station (ISS). Landers, rovers, and orbiter missions support the search for signatures of Life beyond Earth, by generating data on surface and subsurface conditions of other worlds. These have provided evidence for water activity, supporting the potential for extinct or extant Life. To investigate the putative ecologies of these systems, we study extreme environments on Earth. Several locations on our planet provide analog settings to those we have detected or expect to find on neighboring and distant worlds. Whereas, the field of space biology uses the ISS and low gravity analogs to gain insight on how transplanted Earth-evolved organisms will respond to extraterrestrial environments. Modern genomics allows us to chronicle the genetic makeup of such organisms and provides an understanding of how Life adapts to various extreme environments. ! 1 caister.com/cimb Curr. Issues Mol. Biol. Vol. 38 Astrobiology Roadmap O'Rourke et al ! 3 What is the future of life on Earth and elsewhere? Is there life elsewhere in the universe? how did life begin and evolve?

Epidemiological and animal studies have associated systemic inflammation with blood pressure (BP). However, the mechanistic factors linking inflammation and BP remain unknown. Fatty acid derived eicosanoids serve as mediators of inflammation and have been suggested to also regulate renal vascular tone, peripheral resistance, renin-angiotensin system, and endothelial function. We therefore hypothesize that specific pro- and anti-inflammatory eicosanoids are linked with BP. We studied a population sample of 8099 FINRISK 2002 participants randomly drawn from the Finnish population register (53% women, mean age 48±13 years) and, for external validation, a sample of 2859 Framingham Heart Study (FHS) Offspring study participants (55% women, mean age 66±9 years). Using non-targeted liquid chromatography-mass spectrometry, we profiled 545 distinct high-quality eicosanoids and related oxylipin mediators in plasma. Adjusting for conventional hypertension risk factors, we observed 187 (34%) metabolites that were significantly associated with systolic BP (P < Bonferroni-corrected threshold of 0.05/545). We used forward selection linear regression modeling in FINRISK to define a general formula for individual eicosanoid risk score. Individuals of the top risk score quartile in FINRISK had a 9.0 mmHg (95% CI 8.0-10.1) higher systolic BP compared with individuals in the lowest quartile in fully adjusted models. Observed metabolite associations were consistent across FINRISK and FHS. In conclusion, plasma eicosanoids demonstrate strong associations with BP in the general population. As eicosanoid compounds affect numerous physiological processes that are central to BP regulation, they may offer new insights regarding pathogenesis of hypertension, as well as serve as potential targets for therapeutic intervention.

Aim Peptide markers of inflammation have been associated with the development of type 2 diabetes. The role of upstream, lipid-derived mediators of inflammation such as eicosanoids, remains less clear. The aim was to examine whether eicosanoids are associated with incident type 2 diabetes. Methods In the FINRISK 2002 study, a population-based sample of Finnish men and women aged 25-74 years, we used directed, non-targeted liquid chromatography - mass spectrometry to identify 545 eicosanoids and related oxylipins in the participants' plasma samples (n=8,292). We used multivariable-adjusted Cox regression to examine associations between eicosanoids and incident type 2 diabetes. The findings were replicated in the Framingham Heart Study (FHS, n=2,886) and DILGOM 2007 (n=3,905). Together, these three cohorts had 1070 cases of incident type 2 diabetes. Results 76 eicosanoids were associated individually with incident type 2 diabetes. We identified three eicosanoids independently associated with incident type 2 diabetes using stepwise Cox regression with forward selection and a Bonferroni-corrected inclusion threshold. A three-eicosanoid risk score produced a hazard ratio (HR) of 1.56 (95% confidence interval 1.41-1.72) per one standard deviation (SD) increment for risk of incident diabetes. The HR for comparing the top quartile to the lowest was 2.80 (2.53-3.07). Meta-analysis of the three cohorts yielded a pooled HR per SD of 1.31 (1.05-1.56). Conclusion Plasma eicosanoid profiles predict incident type 2 diabetes and the clearest signals replicate in three independent cohorts. Our findings give new information on the biology underlying type 2 diabetes and suggest opportunities for early identification of people at risk.