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Eicosanoid Inflammatory Mediators Are Robustly Associated With Blood Pressure in the General Population.

ABSTRACT: 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

SUBMITTER: Palmu J

PROVIDER: S-EPMC7792391 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Eicosanoid Inflammatory Mediators Are Robustly Associated With Blood Pressure in the General Population.

Palmu Joonatan J Watrous Jeramie D JD Mercader Kysha K Havulinna Aki S AS Lagerborg Kim A KA Salosensaari Aaro A Inouye Mike M Larson Martin G MG Rong Jian J Vasan Ramachandran S RS Lahti Leo L Andres Allen A Cheng Susan S Jousilahti Pekka P Salomaa Veikko V Jain Mohit M Niiranen Teemu J TJ

Journal of the American Heart Association 20200925 19

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 Resu ...[more]

PMID: 32975162

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Project description:Mechanisms that contribute to myocardial fibrosis, particularly in response to left ventricular pressure overload (LVPO), remain poorly defined. To test the hypothesis that a myocardial-specific profile of secreted factors is produced in response to PO, levels of 44 factors implicated in immune cell recruitment and function were assessed in a murine model of cardiac hypertrophy and compared with levels produced in a model of pulmonary fibrosis (PF). Mice subjected to PO were assessed at 1 and 4 wk. Protein from plasma, LV, lungs, and kidneys were analyzed by specific protein array analysis in parallel with protein from mice subjected to silica-instilled PF. Of the 44 factors assessed, 13 proteins were elevated in 1-wk PO myocardium, whereas 18 proteins were found increased in fibrotic lung. Eight of those increased in 1-wk LVPO were not found to be increased in fibrotic lungs (CCL-11, CCL-12, CCL-17, CCL-19, CCL-21, CCL-22, IL-16, and VEGF). Additionally, six factors were increased in plasma of 1-wk LVPO in the absence of increases in myocardial levels. In contrast, in mice with PF, no factors were found increased in plasma that were not elevated in lung tissue. Of those factors increased at 1 wk, only TIMP-1 remained elevated at 4 wk of LVPO. Immunohistochemistry of myocardial vasculature at 1 and 4 wk revealed similar amounts of total vasculature; however, evidence of activated endothelium was observed at 1 wk and, to a lesser extent, at 4 wk LVPO. In conclusion, PO myocardium generated a unique signature of cytokine expression versus that of fibrotic lung.NEW & NOTEWORTHY Myocardial fibrosis and the resultant increases in myocardial stiffness represent pivotal consequences of chronic pressure overload (PO). In this study, cytokine profiles produced in a murine model of cardiac fibrosis induced by PO were compared with those produced in response to silica-induced lung fibrosis. A unique profile of cardiac tissue-specific and plasma-derived factors generated in response to PO are reported.

Dataset Information

Eicosanoid Inflammatory Mediators Are Robustly Associated With Blood Pressure in the General Population.

Publications

Eicosanoid Inflammatory Mediators Are Robustly Associated With Blood Pressure in the General Population.

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