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Eicosanoid inflammatory mediators are robustly associated with blood pressure in the general population
journal contributionposted on 2020-12-21, 06:52 authored by Joonatan Palmu, Jeramie D Watrous, Kysha Mercader, Aki S Havulinna, Kim A Lagerborg, Aaro Salosensaari, Michael InouyeMichael Inouye, Martin G Larson, Jian Rong, Ramachandran S Vasan, Leo Lahti, Allen Andres, Susan Cheng, Pekka Jousilahti, Veikko Salomaa, Mohit Jain, Teemu J Niiranen
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 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.
This work was supported by the Emil Aaltonen Foundation (Niiranen), the Paavo Nurmi Foundation (Niiranen), the Finnish Medical Foundation (Niiranen), the Finnish Foundation for Cardiovascular Research (Salomaa), the Academy of Finland (grant 321351 to Niiranen; grants 295741 and 307127 to Lahti; grant 321356 to Havulinna), Ellison Foundation (Cheng), the National Heart, Lung, and Blood Institute's FHS (Framingham Heart Study) (contracts N01HC25195, HHSN268201500001I, and 75N92019D00031), and the following National Institutes of Health grants: R01HL093328 (Vasan), R01HL107385 (Vasan), R01HL126136 (Vasan), R00HL107642 (Cheng), R01HL131532 (Cheng), R01HL134168 (Cheng and Jain), R01HL143227 (Cheng and Jain), R01ES027595 (Jain and Cheng), and K01DK116917 (Watrous). Dr Vasan is supported in part by the Evans Medical Foundation and the Jay and Louis Coffman Endowment from the Department of Medicine, Boston University School of Medicine. The funders play no role in the design of the study; the collection, analysis, and interpretation of the data; and the decision to approve publication of the finished manuscript. All authors had full access to all of the data (including statistical reports and tables) in the study and can take responsibility for the integrity of the data and the accuracy of the data analysis.
JournalJournal of the American Heart Association
Rights StatementThe Author reserves all moral rights over the deposited text and must be credited if any re-use occurs. Documents deposited in OPAL are the Open Access versions of outputs published elsewhere. Changes resulting from the publishing process may therefore not be reflected in this document. The final published version may be obtained via the publisher’s DOI. Please note that additional copyright and access restrictions may apply to the published version.
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Science & TechnologyLife Sciences & BiomedicineCardiac & Cardiovascular SystemsCardiovascular System & Cardiologyblood pressureeicosanoidshypertensionliquid chromatography-mass spectrometrymetaboliteC-REACTIVE PROTEINSOLUBLE EPOXIDE HYDROLASECORONARY-HEART-DISEASEMENDELIAN RANDOMIZATIONARACHIDONIC-ACID20-HYDROXYEICOSATETRAENOIC ACIDHYPERPOLARIZING FACTORAORTIC STIFFNESSRISK-FACTORSHYPERTENSIONliquid chromatography–mass spectrometry